Pumping systems for cassette-based dialysis

ABSTRACT

A dialysis machine includes: a hardware unit including at least one pump actuator, at least one valve actuator and a cassette interface, the cassette interface including: (i) a plate that abuts the cassette; (ii) at least one pump aperture defined by the plate; (iii) at least one pump head moveable out of and retractable into the at least one pump aperture to operate a pumping portion of the cassette; (iv) at least one valve aperture defined by the plate; (v) at least one valve apparatus moveable out of and retractable into the at least one valve aperture to operate a valve portion of the cassette; (vi) at least one sensor aperture defined by the plate; and (vii) at least one sensor located in the least one sensor aperture, the at least one sensor operable with a sensor portion of the cassette.

PRIORITY

This application claims priority to and the benefit as a continuationapplication of U.S. patent application entitled Pumping Systems forCassette-Based Dialysis, Ser. No. 14/096,904, filed Dec. 4, 2013, nowU.S. Pat. No. 8,740,837, issued Jun. 3, 2014, which is a divisionalapplication of U.S. patent application entitled Pumping Systems forCassette-Based Dialysis”, Ser. No. 13/528,502, filed Jun. 20, 2012, nowU.S. Pat. No. 8,679,054, issued Mar. 25, 2014, which claims priority toand the benefit as a continuation application of U.S. patent applicationentitled “Pumping Systems For Cassette-Based Dialysis”, Ser. No.11/773,148, filed Jul. 3, 2007, now U.S. Pat. No. 8,206,338, issued Jun.26, 2012, which claims priority to and the benefit as a continuationapplication of U.S. patent application entitled “System IncludingMachine Interface For Pumping Cassette-Based Therapies”, Ser. No.11/617,527, filed Dec. 28, 2006, now U.S. Pat. No. 7,867,189, issuedJan. 11, 2011, which claims priority to and the benefit as acontinuation application of U.S. patent application entitled “SystemIncluding Machine Interface For Pumping Cassette-Based Therapies”, Ser.No. 10/335,646, filed Dec. 31, 2002, now U.S. Pat. No. 7,238,164, issuedJul. 3, 2007, which claims priority to and the benefit of U.S.Provisional Application Ser. Nos. 60/397,045 and 60/397,268, filed Jul.19, 2002.

BACKGROUND OF THE INVENTION

The present invention generally relates to medical fluid systems. Morespecifically, the present invention relates to systems and methods ofperforming cassette-based dialysis and devices related thereto.

Due to various causes, a person's renal system can fail. Renal failureproduces several physiological derangements. The balance of water,minerals and the excretion of daily metabolic load is no longer possibleand toxic end products of nitrogen metabolism (urea, creatinine, uricacid, and others) can accumulate in blood and tissues.

Kidney failure and reduced kidney function have been treated withdialysis. Dialysis removes waste, toxins and excess water from the bodythat would otherwise have been removed by normal functioning kidneys.Dialysis treatment for replacement of kidney functions is critical tomany people because the treatment is life saving.

Hemodialysis and peritoneal dialysis are two types of dialysis therapiesused commonly to treat loss of kidney function. Hemodialysis treatmentutilizes the patient's blood to remove waste, toxins and excess waterfrom the patient. The patient is connected to a hemodialysis machine andthe patient's blood is pumped through the machine. Catheters areinserted into the patient's veins and arteries so that blood can flow toand from the hemodialysis machine. The blood passes through a dialyzerof the machine, which removes waste, toxins and excess water from theblood. The cleaned blood is returned to the patient. A large amount ofdialysate, for example about 120 liters, is consumed to dialyze theblood during a single hemodialysis therapy. Hemodialysis treatment lastsseveral hours and is generally performed in a treatment center aboutthree or four times per week.

Peritoneal dialysis uses a dialysis solution or “dialysate”, which isinfused into a patient's peritoneal cavity via a catheter. The dialysatecontacts the peritoneal membrane of the peritoneal cavity. Waste, toxinsand excess water pass from the patient's bloodstream, through theperitoneal membrane and into the dialysate due to diffusion and osmosis,i.e., an osmotic gradient occurs across the membrane. The spentdialysate is drained from the patient, removing waste, toxins and excesswater from the patient. This cycle is repeated.

There are various types of peritoneal dialysis therapies, includingcontinuous ambulatory peritoneal dialysis (“CAPD”), automated peritonealdialysis (“APD”), including tidal flow APD and continuous flowperitoneal dialysis (“CFPD”). CAPD is a manual dialysis treatment. Thepatient connects manually an implanted catheter to a drain, allowingspent dialysate fluid to drain from the peritoneal cavity. The patientthen connects the catheter to a bag of fresh dialysate, infusing freshdialysate through the catheter and into the patient. The patientdisconnects the catheter from the fresh dialysate bag and allows thedialysate to dwell within the peritoneal cavity, wherein the transfer ofwaste, toxins and excess water takes place. After a dwell period, thepatient repeats the manual dialysis procedure, for example, four timesper day, each treatment lasting about an hour. Manual peritonealdialysis requires a significant amount of time and effort from thepatient, leaving ample room for improvement.

Automated peritoneal dialysis (“APD”) is similar to CAPD in that thedialysis treatment includes drain, fill, and dwell cycles. APD machines,however, perform the cycles automatically, typically while the patientsleeps. APD machines free patients from having to manually perform thetreatment cycles and from having to transport supplies during the day.APD machines connect fluidly to an implanted catheter, to a source orbag of fresh dialysate and to a fluid drain. APD machines pump freshdialysate from the dialysate source, through the catheter, into thepatient's peritoneal cavity and allow the dialysate to dwell within thecavity and the transfer of waste, toxins and excess water to take place.APD machines pump spent dialysate from the peritoneal cavity, though thecatheter, to the drain. As with the manual process, several drain, filland dwell cycles occur during APD. A “last fill” occurs at the end ofCAPD and APD, which remains in the peritoneal cavity of the patientuntil the next treatment.

Both CAPD and APD are batch type systems that send spent dialysis fluidto a drain. Tidal flow systems are modified batch systems. With tidalflow, instead of removing all the fluid from the patient over a longerperiod of time, a portion of the fluid is removed and replaced aftersmaller increments of time.

Continuous flow or CFPD systems clean or regenerate spent dialysateinstead of discarding it. The systems flow fluid into or out of thepatient, through a loop. Dialysate flows into the peritoneal cavitythrough one catheter lumen and out another catheter lumen. The fluidexiting the patient passes through a reconstitution device that removeswaste from the dialysate, e.g., via a urea removal column that employsurease to enzymatically convert urea into ammonia. The ammonia is thenremoved from the dialysate by adsorption prior to reintroduction of thedialysate into the peritoneal cavity. Additional sensors are employed tomonitor the removal of ammonia. CFPD systems are more complicatedtypically than batch systems.

Hemodialysis, APD (including tidal flow) and CFPD systems can employ apumping cassette. The pumping cassette typically includes a flexiblemembrane that is moved mechanically to push and pull dialysis fluid outof and into, respectively, the cassette. Certain known systems includeflexible sheeting on one side of the cassette, while others includesheeting on both sides of the cassette. Positive and/or negativepressure can be used to operate the pumping cassettes.

One problem with the pumping cassettes is leakage. If the flexiblemembranes experience a pinhole or tear, fluid and air can move from oneside of the membrane to the other. Movement of fluid from inside thecassette to the inner workings of the machine can damage the machine.Movement of air from the machine into the cassette can compromise thesterility of the fluid pathways defined by the cassette. There aredetection systems that determine when fluid leaks from the cassette tothe machine. It is more difficult, however, to detect fluid leaking intothe cassette.

Another problem with cassette-based pumping occurs when the cassette isloaded improperly into the machine. Proper alignment is importantbecause portions of the flexible membrane must match correspondingmachine portions, e.g., pump and valve actuators Improper loading canlead to undue mechanical stress being placed on the cassette, harmingpotentially the cassette and/or the actuator. Improper cassette loadingwill also likely degrade or prohibit performance of the system.

A further dilemma, especially in CFPD, is the coordination of multiplefluid delivery. Cassette-based peritoneal pumping systems thatadminister fluids continuously to patients are required to withdrawfluid (ultrafiltrate) from and add fluid (concentrate) to a continuouslyflowing dialysis fluid loop. The additional fluids have typicallynecessitated additional dedicated pumps, which make the cassette anddialysis machine larger and noisier. Scheduling the operation ofmultiple pumps also presents a challenge to system implementers.

Another problem associated with cassette-based pumping is the entrapmentof air or other gas into the fluid pathways. Air can enter the systemvia leaking connections, improper priming, faulty tubing and faultycassettes. Patient therapy also produces various gases that enter thesystem. Cassette-based pumps are designed to pump fluid, not gas.Moreover, the removal and delivery of fluid from and to the patientneeds to be monitored and controlled. Air and gases upset volumemeasurement systems that assume no air or gas exists in the fluidpathways. Air and gases can also be uncomfortable for the patient andimpede proper waste removal.

It is desirable to remove air and gas from the dialysis fluid before thefluid enters the patient. To this end, cassette-based systems have beenprovided with air or gas vents. A need continues however to provide formore economical venting systems. Further, prior to infusion, thedialysis fluid solution is heated to body temperature, releasing gasfrom the solution. Known vents do not vent air or gas due to fluidheating. It is also desirable to have a method for detecting air andfluid, so that the volume of both can measured, detecting air forpurging and detecting fluid for ensuring proper therapy.

SUMMARY OF THE INVENTION

In general, the present invention relates to medical fluid deliverysystems that employ a pumping cassette. In particular, the presentinvention provides systems, methods and apparatuses for cassette-baseddialysis therapies including hemodialysis, CAPD, APD (including tidalmodalities) and CFPD, as these therapies have been described above.

In one embodiment, the systems, methods and apparatuses of the presentinvention are used with CFPD. The CFPD therapy includes, generally, afluid circuit or loop connected to a patient, allowing dialysate orother suitable therapy fluid to be circulated into, through and out ofthe patient's peritoneal cavity to remove a therapeutic effective amountof excess water and solutes, such as uremic toxins, urea, creatinine andthe like.

In an embodiment, the dialysate is continuously circulated along thefluid loop multiple times prior to discharge. The volume of dialysateconsumed is minimized with respect to batch systems. The circulation cantake the form of a single pass or multiple passes. One single passsystem operable with the cassette-based systems, methods and apparatusesof the present invention is described in document Ser. No. 10/623,317.One multiple pass system operable with the cassette-based systems,methods and apparatuses of the present invention is described indocument Ser. No. 10/624,150.

As discussed above, the present invention is not limited to CFPD. OneAPD system operable with the cassette-based systems, methods andapparatuses of the present invention is described in U.S. patentapplication Ser. No. 10/155,603, Publication No. 20030220598, publishedNov. 27, 2003, entitled, “Automated Dialysis System,” the teachings ofwhich are incorporated herein by reference. With these types of dialysissystems in mind, some of the various embodiments of the presentinvention are hereafter summarized.

In one embodiment, the present invention provides an actuator assemblythat operates with the disposable cassette. The assembly includes ahousing that holds both the pump actuators and the valve actuators. Thepump/valve manifold eliminates the need for separate valve manifolds.This in turn reduces significantly the amount of tubing and tubingconnections that would otherwise have to be made between one or morevalve manifolds and a pump actuator housing. The combination pump/valvemanifold also conserves space and materials, allowing for a smaller,lighter and more cost effective dialysis machine.

In another embodiment of the present invention, a fail safe valve andpump arrangement is provided. The arrangement allows fluid to flow onlyfrom the cassette into the machine in the event of a cassette failure. Apositive pressure gradient is maintained from the cassette to themachine, generally preventing air from entering the cassette. Thearrangement also ensures that all valves close in the event of a systemfailure or power failure, preventing fluid from mixing across fluidpathways in the cassette.

The arrangement includes a disposable cassette operable with one or morediaphragm pump chambers, one or more diaphragm valve seats and one ormore fluid pathways. The cassette is constructed of a rigid orsemi-rigid body portion (referred to collectively herein as “rigidportion”) having flexible sheeting sealed to one or both sides of theportion. The cassette with sheeting is mated with at least one pump andat least one valve driver mechanism, creating an interconnected fluidicssystem.

During operation, a vacuum is normally maintained between the cassettesheeting and the pump/valve driver interface wherever a pump, valve, orfluid pathway is created. This creates a positive pressure gradient fromthe cassette to the components of the dialysis machine. The valveplungers press the sheeting against the rigid portion of the cassette,closing the valves unless a vacuum (or pressure) is provided tomechanisms that retract the valve plungers.

The pump actuators may be configured to extend, retract or hold positionin the event of system failure and include a piston having a pistonhead. The piston head pushes against a flexible membrane of thedisposable cassette to dispel fluid from the cassette. Various actuatorsare provided to move the piston heads. One actuator, for example,includes a first or deep vacuum that draws the piston head away from thecassette and a second shallow vacuum that pulls the membrane away fromthe cassette, causing dialysis fluid to enter the cassette. In anembodiment, a spring cavity is located on the end of the piston oppositethe piston head. The spring cavity houses a spring, which when the deepvacuum is not present, pushes the piston, piston head and cassette sheetinto the rigid portion of the cassette. When the deep vacuum is applied,the deep vacuum overcomes the compression resistance of the spring andcompresses the spring.

To separate the deep and shallow vacuums, a rolling diaphragm is sealedto the pump piston and the walls of the spring housing. The rollingdiaphragm includes enough take-up material to allow the piston to moveback and forth. To ensure that the take-up material of the diaphragmrolls or moves properly, a shallow vacuum is left in the spring housing(i.e., in place of the deep vacuum) when the deep vacuum is removed. Theshallow vacuum is not strong enough to overcome the compressionresistance of the spring but is strong enough to keep the rollingdiaphragm from inverting due to the shallow vacuum maintained around thepiston head that seals the membrane to the piston head. Alternatively,multiple rolling diaphragms are used, with atmospheric air appliedbetween the diaphragms.

One alternative valve actuator replaces the diaphragm with apiston-cylinder, which is activated via negative or positive pressure.Another alternative valve actuator replaces the diaphragm, spring anddeep vacuum altogether with an electrically operated actuator, such as astepper motor (linear or rotary), servo motor or other type of linearactuator. A shallow vacuum is still applied to seal the cassettemembrane to the piston head.

A fail safe valve is also provided, which makes use of the deep andshallow vacuum in an embodiment. The valve utilizes a spring andnegative pressure to operate a valve plunger that contacts the flexiblemembrane of the disposable cassette. The valve also seals to a moveablediaphragm that separates different vacuums. A deep vacuum is applied tocompress the spring, moving the valve plunger away from the cassette. Ashallow vacuum is applied to the opposite side of the diaphragm from thespring housing and causes the flexible membrane of the cassette to movewith the valve plunger. The shallow vacuum also aids the spring to pushthe plunger against the flexible membrane, increasing the valve sealingforce. The deep vacuum is strong enough therefore to overcome thespring's compression resistance and the shallow vacuum.

In a further embodiment of the present invention, a method and apparatusfor automatically aligning the disposable cassette within the machine isprovided. The procedure attempts to correct smaller misalignments, sendsan error for larger misalignments, helps to ensure cassette quality andprovides cassette integrity testing.

The method includes loading the cassette into the dialysis machine and,before inflating a sealing bladder, moving one or more pump pistontowards a respective pump cavity. This action causes the cassette toshift, if need be, into its proper position. If a resistance to themovement of the piston(s) is detected, the dialysis machine knows that aproblem has occurred either with the cassette or the mechanics of themachine and can take action appropriately. The procedure is operablewhether the cassette loads horizontally on top of the machine, orvertically on a side of the machine.

After the alignment procedure takes place, a bladder inflates andcompresses the cassette against an inner surface of the dialysismachine, the pump pistons and valve plungers. The cassette is then readyfor use. A sensor is also provided, such as a strain gauge, whichmonitors the force exerted by the moving pistons on the cassette. If thedisposable cassette is out of alignment to the point that alignmentcannot be corrected, the sensor detects the undue stress placed on thepiston head, sends an error message and de-energizes the pumps.

In yet another embodiment of the present invention, a material for theflexible membrane is provided. The material is fabricated from a non-PVCcontaining, thermoplastic polymeric material and can be of a monolayerstructure or a multiple layer structure. The film can be fabricatedusing standard thermoplastic processing techniques such as extrusion,coextrusion, extrusion lamination, lamination, blown extrusion, tubularextrusion, cast extrusion or coextrusion, compression molding andthermoforming.

In still a further embodiment of the present invention, a valvearrangement is provided that allows different fluids to be combined andremoved from a medical fluid system. The valve arrangement is operablewith a single pump or multiple fluid pumps. The arrangement is describedin connection with CFPD but is operable with other types of dialysis. Inthe illustrated embodiment, the arrangement allows concentrate to beadded and ultrafiltrate to be withdrawn from a dialysis fluid in acontinuous or semi-continuous manner, without requiring additional fluidpumps.

The valve arrangement adds an additional inlet valve and outlet valvefor each pump. To this end, each pump operates with a main intake valvethat provides on/off control for the inlet flow of dialysate in acontinuous loop (CFPD) or from a supply bag (APD). A second intake valveoperates in parallel with the main intake valve and provides on/offcontrol for a concentrate or additive (CFPD) or parallel dialysatesupply (APD). Each pump operates with a main exhaust valve that provideson/off control for the outlet flow of dialysate, e.g., to the patient. Asecond exhaust valve operates in parallel with the main outlet valve andprovides on/off control for, e.g., the removal of ultrafiltrate from thedialysis fluid.

When the second intake and exhaust valves are open, the main valves areclosed and vice versa in an embodiment. The relevant amount of time thatthe main versus the second valves are open determines how quicklyconcentrate is added or ultrafiltrate is removed. For instance one pumpvolume's worth of concentrate can be pumped once every thirty-three pumpstrokes or once every five-hundred pump strokes.

In one implementation, a pair of multiplexed pumps is provided, yieldingalternating and virtually continuous flow of fluid to the patient. Inthis implementation, a number of variations arise. For example, thesecondary intake valves or the secondary exhaust valves can be openedsimultaneously, doubling concentrate intake or ultrafiltrate removal.Still further, partial fills can be employed via the second valves byonly partially moving the pump piston.

In still a further embodiment of the present invention, an expert systemand method for scheduling the pumping of one or more solutions, via oneor more pumps and to one or more destinations is provided. The systemand method are illustrated with respect to CFPD but are also applicableto APD and hemodialysis. The expert system uses a set of rules. Therules are derived from physical limitations, e.g., fluid flowconnections and pumping state limitations. The rules are also derivedfrom therapy limitations, e.g., it is undesirable to pump concentratedirectly to ultrafiltrate collection, and arbitrary limitations, e.g.,no partial pump strokes.

The expert system also accounts for a number of parameters inputted bythe patient or doctor. The system applies various algorithms to theinputted values to yield the output requirements for the therapy, e.g.,overall flow volume, flowrate, therapy time, total concentrate added,etc. Using the outputs and the rules or restrictions, the expert systemdevelops a pumping schedule having a number of entries. Each entrydirects one or more pump to pull or push from one or more solution or toone or more destination, respectively. The controller of the systemcommands the pumps to execute the pumping profile set forth in theschedule. The schedule may represent a portion of the overall therapy,wherein the schedule is cycled a number of times until therapy iscomplete. In the end, the outputs are achieved according to the rulesand other limitations, such as fluid pressure level limitations.

In yet another embodiment of the present invention, a port vent forventing air purged from the dialysis fluid is provided. The port vent isintegral to the cassette and vents the priming volume as well as airentrained due to pumping and patient exhaust gases. The cassette-basedport vent is molded integrally with the rigid portion of the cassette,taking advantage of the fact that the rigid portion is otherwise amolded structure. A filter, such as a 0.2 micron filter is then fixed,e.g., bonded, heat sealed, adhered or mechanically fixed, to the portvent. The filter is made of a material, such as PTFE, Gortex or otherpolymer, which can be bonded, heat sealed, adhered or fixedmechanically. In an embodiment, the filter is made of a hydrophobicmaterial. Alternatively, the filter is bonded, heat sealed, adhered orfixed to a bushing that fits onto and is suitably attached to the moldedport.

Moreover, in an embodiment an additional air separation chamber for amedical fluid system is provided. The cassette-based port vent providesa first venting mechanism that separates air entrained in the fluid atthe point of pumping. After the dialysis fluid leaves the pumpingcassette, however, the fluid passes through a heater. The addition ofheat releases gas trapped in the solution. This additional released gasmust also be purged before the solution enters the patient.

The additional gas separation chamber is located downstream from thefluid heater. The heat released gas rises to and is trapped at the topof the chamber, while the heated fluid passes through the bottom of thechamber. The chamber houses one or more capacitive sensors that detectthe amount of gas in the chamber. When the amount reaches apredetermined level, one or more exhaust valve opens and allows the gasto vent.

The gases vent through a membrane. To keep the membrane dry, a series ofexhaust valves may be employed. To this end, a sump fluid trap mayalternatively or additionally be provided.

In still another embodiment, a gas separation device is provided thatincludes a series of valves that are operated sequentially. A fluid trapis provided in between the valves. The sequential operation of thevalves and trap enables gas but not fluid to escape from the system.

In consideration of the embodiments described herein, it is therefore anadvantage of the present invention to provide a cassette actuatorassembly that houses both the pump and valve actuators.

Another advantage of the present invention is to provide acassette-based medical fluid system having fail safe valve and pumpactuation.

A further advantage of the present invention is to provide acassette-based medical fluid system having a positive pressure gradientbetween the cassette fluid pathways and the outlying components of thedialysis machine.

Still another advantage of the present invention is to provide acassette-based medical fluid system having a cassette auto-alignmentfeature.

Yet another advantage of the present invention is to provide acassette-based medical fluid system having a cassette misalignmentoutput and a cassette integrity feature.

Moreover, an advantage of the present invention is to provide animproved material for the flexible membrane of the cassette.

Still further, an advantage of the present invention is to provide acassette-based medical fluid system having a multiplexing valvearrangement.

Further still, an advantage of the present invention is to provide acassette-based medical fluid system having an expert fluid pumpingmanagement system that uses a knowledge base to derive a pumpingschedule after parameters are inputted by a doctor/patient.

Still a further advantage of the present invention is to provide acassette-based integrally formed port vent.

Yet a further advantage of the present invention is to provide an airseparation chamber downstream of a medical fluid heater.

Moreover, a further advantage of the present invention is to allow thedialysis fluid to purge entrained gas while the fluid is being pumped.

Additional features and advantages of the present invention aredescribed in, and will be apparent from, the following DetailedDescription of the Invention and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1 and 2 illustrate opposing views of an embodiment of a value andpump actuation assembly having a value/pump housing that houses incombination a valve manifold and a plurality of pump actuators.

FIG. 3 is a perspective view of one embodiment of a valve actuator usedin the present invention.

FIG. 4 is a perspective view of a surface of the valve/pump housingillustrated in FIG. 1 that remains after a portion of the housing iscutaway, the surface showing vacuum and atmospheric air flow paths.

FIG. 5 is a perspective view of the opposing side of the valve/pumphousing from the side illustrated in FIG. 4, the opposing side showing aplurality of valve plunger cavities.

FIG. 6 is a sectioned elevation view of mechanically and pneumaticallyoperated pumps of the present invention shown in combination with afluid pumping cassette.

FIG. 7 is a sectioned elevation view of another embodiment ofmechanically and pneumatically operated pumps of the present inventionshown in combination with a fluid pumping cassette.

FIG. 8 is a sectioned elevation view of electrically operated pumps ofthe present invention connected operably to a fluid pumping cassette.

FIG. 9 is a sectioned elevation view of a further alternative embodimentof a pneumatically and mechanically operated pump of the presentinvention.

FIGS. 10 and 11 are sectioned elevation views of one embodiment of apneumatically and mechanically actuated valve of the present invention.

FIG. 12 is a perspective view of a dialysis hardware machine showing theloading of a disposable cassette and an embodiment of an auto-alignmentfeature of the present invention.

FIGS. 13 and 14 are sectioned elevation views taken through linesXIII-XIII and XIV-XIV, respectively, in FIG. 12 illustrating thecassette auto-alignment feature of the present invention.

FIGS. 15 and 16 illustrate various embodiments of an improved membranepumping material of the present invention.

FIGS. 17 to 20 illustrate an embodiment for a valve arrangement of thepresent invention allowing multiple fluids to be pumped into and out ofthe same fluid pump chamber.

FIG. 21 is a schematic process flow diagram illustrating various fluidflow connections between a plurality of solutions, a plurality of pumpsand a plurality of fluid destinations for an expert pumping system ofthe present invention.

FIG. 22 is a diagram that illustrating schematically the possible statesof the fluid pumps for the expert pumping system of the presentinvention.

FIG. 23 is a sample list of software rules implemented to control theflow for the expert pumping system of the present invention.

FIG. 24 shows schematic diagrams illustrating pumping modules that arepart of the outcome of the fluid flow connections of FIG. 21, a statediagram of FIG. 22 and the software rules implemented in FIG. 23.

FIGS. 25 and 26 are process flow diagrams illustrating schematically anembodiment of the expert pumping system and method of the presentinvention.

FIGS. 27 to 29 illustrate various inputs, outputs and algorithms used bythe expert pumping system of the present invention to output a fluidflow schedule illustrated in FIG. 30.

FIG. 30 is a table showing a portion of a fluid flow schedule of theexpert pumping system and method of the present invention, the scheduleorganizing the flow of fluid from various pumps to achieve desired flowrates and volumes of various fluids to various destinations over adesired period of time.

FIG. 31 is a cutaway perspective view of a rigid portion of a disposablecassette showing various embodiments for a port vent of the presentinvention.

FIG. 32 is a sectioned elevation view of one embodiment of an airseparation chamber using capacitance fluid volume sensing.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to cassette based medical fluid deliverysystems. In particular, the present invention provides variousimprovements to the cassette and components operating with the cassette,in fluid communication with the cassette or in connection with managingthe flow of fluids through the cassette in complex systems having amultitude of fluid sources, a multitude of fluid pumps and a multitudeof fluid destinations. These improvements are particularly well suitedtherefore for CFPD, which is typically more complex than other forms ofdialysis treatment. It is expressly contemplated however that theembodiments set forth are not limited to CFPD and are operable with APD(including tidal flow systems), hemodialysis, hemofiltration and anycombination thereof.

I. Combined Pump and Valve Housing

Referring now to the drawings and in particular to FIGS. 1 to 5, acombination valve manifold and pump housing assembly 10 is illustrated.FIGS. 1 and 2 illustrate that assembly 10 includes a number ofcomponents, including a valve/pump housing 20, a number of intermediateplates 24 and 26 and a front plate 30. Assembly 10 in other embodimentscan have less or more than four components depending upon the complexityof the medical fluid system, for example, depending on the number andtype of pumps and the number and type of fluid valves.

The assembly 10 is housed inside of an automated peritoneal dialysismachine, wherein the valve/pump housing 20 and the components mounted tothe housing face inward towards the center of the machine. The frontplate 30 faces upward and outward toward the disposable cassette (seeFIG. 12 showing machine 100 and cassette 150). A number of bolts orother type of fastening devices 22 hold housing 20, intermediate plates24 and 26 and front plate 30 together. Mounting devices 22 can also boltassembly 10 to the dialysis machine in an embodiment.

A gasket may also be placed between any mating component, such asbetween the valve/pump housing 20 and intermediate plate 24, betweenintermediate plates 24 and 26 and/or between intermediate plate 26 andfront plate 30. As illustrated below in connection with FIGS. 6, 7 and 9to 11, one or more vacuum chambers are used in various embodiments inconnection with the valves and the pumps of the present invention. Aportion of the vacuum chambers is defined by apertures collectively madeby one or more or all of the housing 20 and plates 24, 26 and 30,requiring an airtight seal between these components. In an embodiment, anegative pressure of about −2 to −20 psig. and preferably about −6 psig.to about −10 psig. is applied within the vacuum chambers. The gasketsbetween components 20, 24, 26 and 30 are selected and sized to withstandthis level of vacuum.

FIG. 1 illustrates that three pump actuators 32 mount to the valve/pumphousing 20, however, alternative embodiments of the present inventionmay use one pump, two pumps or more than three pumps. Pump actuators 32in an embodiment are linear motors, such as linear stepper motors madeby Hayden Switch and Instrument Inc., Waterbury, Conn. FIGS. 6 and 7illustrate that the pump actuators are alternatively springs. In furtheralternative embodiments, the pump actuators could be piston cylindersdriven by positive or negative pressure, rotary motors in combinationwith a rotational to linear motion converter or other type of linearmotion producing device.

As illustrated below, and as seen in FIG. 2 on front plate 30, theoutput of the pump actuator is a pump piston 34 having a pump pistonhead 36. Pump actuator 32 pulls piston heads 36 back from the face offront plate 30 towards valve/pump housing 20, pulling via a vacuum aflexible membrane of the disposable cassette (not shown), which in turnpulls dialysis fluid into the cassette. Pump actuators 32 push piston 34and piston head 36 outward from the face of front plate 30, pushing onthe flexible membrane in towards a rigid portion of the cassette todispel fluid from the cassette. As illustrated in FIG. 2, the pistonhead 36 is in a retracted or pulled back position for the outer twopumps and is in a pushed forward position for the middle pump.

The pistons 34 and piston heads 36 each define a vacuum channel 38 in anembodiment. Vacuum channels 38 allow a vacuum applied beneath frontplate 30 to communicate fluidly through the piston 34 and piston head 36with the flexible membrane of the disposable cassette. Alternatively,the vacuum extends around the piston head 36, which is disposed in avacuum chamber, to seal the membrane to piston head 36.

A plurality of valves 40 also mount to the valve/pump housing 20 asillustrated by FIG. 1. Valves 40 are actuated electrically in anembodiment, however, valves 40 can be pneumatically operated in analternative embodiment. FIG. 2 illustrates that a valve plunger 42 isoperable with each of the valves 40. As illustrated in more detail belowin connection with FIGS. 10 and 11, valve plungers 42 are pressedmechanically against the flexible membrane of the disposable cassette,for instance by a spring. The valve plungers are retracted away from theflexible membrane of the disposable cassette via negative pressurefacilitated by valves 40.

Valve plungers 42 also define vacuum orifices in an embodiment thatenable a vacuum to pull the flexible membrane outward, i.e., to open afluid flow path in the disposable cassette, when the valve plunger 42 isretracted or pulled inward from the face of plate 30. Plunger 42 isretracted when pneumatic valve 40 is energized, allowing the spring tosee negative pressure, compressing the spring. The vacuum alternativelyflows around the valve plunger to seal the membrane to the plunger 42.

Referring now to FIG. 3, an embodiment of a pneumatic valve 40 isillustrated. Suitable three port valves are provided by Pneutronics,Inc. of Hollis, N.H., Fluid Automation Systems (FAS) of Versoix, Suisse,SMC Pneumatics and Lee Corporation.

Valve 40 has a housing defining a normally closed or vacuum port 44, acommon or plunger port 46 and a normally open or atmospheric air port48. The common port 46 connects fluidly to a vacuum chamber foroperating the valve plunger 42, for example, vacuum chamber 144illustrated in FIG. 10.

In an embodiment, an open fluid flow path exists when no voltage issupplied to electrical lines V+ and V− between the atmospheric air port48 and the plunger port 46. Pneumatic valve 40 is therefore normallyopen between ports 46 and 48. When a voltage is placed across electricallines V+ and V−, a solenoid within valve 40 is energized so that thefluid path across 46 and 48 is closed and so that a fluid pathway opensbetween vacuum port 44 and plunger port 46.

With valve 40, a fluid pathway in the cassette is opened when a voltageis applied to lines V+ and V−, for example, +−5 VDC or +−24 VDC. Uponenergizing, a vacuum supply evacuates air from a chamber defined byplunger port 46, an aperture defined by valve/pump housing 20, matingapertures in plates 24, 26 and 30, to activate a valve plunger 42 fittedwithin the vacuum chamber. A separate vacuum pulls the cassette membraneoutward from the disposable cassette when the valve plunger 42 isretracted.

When the voltage is removed from electrical lines V+ and V−, thesolenoid returns to its normal state. Atmospheric air is drawn into thevacuum chamber through ports 48 and 46, allowing a valve spring to pushthe valve plunger against the flexible membrane of the disposablecassette, closing the associated fluid pathway

The valve springs are sized appropriately to provide the desired amountof sealing pressure. The spring force in an embodiment is between 0 and10 lbs., and in one preferred embodiment about two to six lbs.

FIG. 1 illustrates that a plurality of different types of fluidconnectors are attached to valve/pump housing 20. Connectors can be anytype of tubing or piping connectors known to those of skill in the art,such as hose barbs, nut and ferrule type connectors, threadedconnectors, quick disconnect type connectors, etc. Connectors 50 connectto negative pressure supply tubes that run to a source of negativepressure (not illustrated). Negative pressure connectors 50 connectfluidly to negative pressure supply channel 60 defined by surface 64 ofhousing 20 as illustrated in FIG. 4.

A plurality of atmospheric air inlet connectors 52 are also mounted tovalve/pump housing 20. Atmospheric air connectors 52 attach to tubesthat connect fluidly to one or more air filters. The filtered air runsthrough connectors 52 to an atmospheric air supply channel 62 defined bythe valve/pump housing 20 illustrated in FIG. 4. Negative supply channel60 feeds each of the vacuum ports 44 of the valve 40 (FIG. 3), whileatmospheric air supply channel 62 feeds each of the atmospheric airports 48 of the pneumatic valve 40. In an embodiment, to evenlydistribute the vacuum, a negative pressure connector 50 is placed neareach of the ends of the negative pressure channel 60, while theatmospheric air inlet connectors 52 are spaced suitably apart along theatmospheric air supply channel 62.

FIG. 1 illustrates that valve/pump housing 20 defines or is attached inan airtight manner to a raised bridge 58. Valves 40 and various ones ofthe connectors 50 and 52 mount to raised bridge 58. Raised bridge 58allows the valve 40 to sit slightly above channels 60 and 62, so thatports 44 and 48 of the valve 40, respectively, can extend into channels60 and 62. A suitable gasket may be placed about channels 60 and 62between the surface 64 (FIG. 4) of housing 20 and bridge 58. Otherwise,bridge 58 is formed integrally with housing 20 or is permanentlyattached, e.g., welded, to housing 20.

FIG. 4 illustrates housing 20 with the bridge 58 removed, exposingchannels 60 and 62 defined in surface 64. Removing bridge 58 alsoexposes various apertures defined by housing 20. For example, housing 20defines a plunger aperture 66 for each pneumatic valve 40. The plungerport 46 of valve 40 (FIG. 3) extends into apertures 66. The gasket (notillustrated) surrounding channels 60 and 62 also surrounds each of theplunger apertures 66 in an embodiment. Plunger apertures 66 allownegative pressure or atmospheric air to extend from inner surface 64 ofhousing 20 to the valve plunger side of housing 20, illustrated in FIG.5. It should be appreciated that the vacuum is supplied throughconnectors 50, through channel 60, through vacuum port 44, throughplunger port 46, through plunger apertures 66 and through correspondingapertures defined by one or more of the plates 24 and 26 and front plate30 to compress the plunger spring and open a fluid pathway in thedisposable cassette. As illustrated below, the vacuum can also bebounded or housed in part by a flexible diaphragm, existing for examplebetween two of the plates 24, 26 and 30.

Valve/pump housing 20 also defines valve sheeting apertures 68. Valvesheeting apertures 68 communicate fluidly with negative pressureconnectors 56 illustrated in FIG. 1. Negative pressure connectors 56communicate fluidly with a negative pressure source and enable a vacuumto be applied through the orifices of the valve plungers 42 (or aroundvalve plungers 42) to the flexible membrane of the disposable cassette.The negative pressure source (not illustrated) pulls a vacuum throughthe connectors 56, through the valve sheeting apertures 68 and throughthe valve plungers 42 to seal the flexible membrane to the valveplungers.

Similar to the negative pressure for the valve sheet, valve/pump housing20 defines, for each fluid pump, a pump sheeting aperture 72. Pumpsheeting apertures 72 communicate fluidly with negative pressure inletconnectors 54, which in turn communicate fluidly with a negativepressure source (not illustrated). The negative pressure source pulls avacuum through connectors 54, through apertures 72, through or aroundthe piston 34 and piston head 36 to seal the flexible membrane of thedisposable cassette to the piston head.

It should be appreciated that three separate vacuums in an embodimentare applied in connection with the valve/pump housing 20 of assembly 10.Namely, a first vacuum is applied to vacuum channel 60 defined bysurface 64 of housing 20, a second vacuum is applied to seal theflexible membrane to the valve plungers and a third vacuum is applied toseal the flexible membrane to the pump piston heads 36. The fluid flowsystem can provide multiple vacuum sources that operate each of thesevacuums separately. Alternatively, one or more sources operate thesevacuums sequentially. Further alternatively, the level of vacuum is thesame for two or more of the required vacuums, wherein a single vacuumsource can supply at least two of the vacuums simultaneously.

FIGS. 1 and 2 illustrate that assembly 10, including valve/pump housing20, houses various types of sensors 74. The various types of sensorsinclude but are not limited to pressure sensors, temperature sensors,liquid level sensors, air detection sensors, bubble sensors, volumemeasurement sensors, conductivity sensors, pH sensors, turbiditysensors, color detection sensors, particle sensors, and chemicalsensors, etc. As illustrated, sensors 74 extend through housing 20,intermediate plates, 24 and 26 and front plate 30. Sensor wiring andsensing leads extend into the dialysis machine from valve/pump housing20. Sensing heads or sensor portions are located flush approximatelywith the face of front plate 30 and contact the disposable cassette tosense a fluid parameter of the dialysis fluid flowing through thecassette. A seal is made in an embodiment between the cassette and thefront plate 30 around the sensors so that a vacuum can be applied,bringing the cassette membrane into intimate contact with the sensors.The vacuum is provided through assembly 10 around the sensors in amanner similar to that provided between the valve plungers 42 and thecassette membrane.

Referring to FIG. 5, the valve/pump housing 20 is illustrated showingsurface 76, which opposes surface 64 illustrated above in connectionwith FIG. 4. For reference, a majority of the plunger apertures 66 thatcommunicate with the plunger port 46 of pneumatic valve 40 areillustrated, as are the pump sheeting apertures 72 that communicatefluidly with the negative pressure inlet connectors 54. At least some ofthe valve plunger apertures 66 are located in the middle of cavities orcraters 78 defined by surface 76 of housing 20. Housing 20, definingcavities 78, is made in various embodiments of molded plastic oraluminum composite. Cavities or craters 78 enable the plungers andplunger seats (not illustrated) to situate properly with respect toplunger apertures 66. For reference, a plunger spring 70 is illustratedcentered about an aperture 66, which in turn is centered in one of thecavities 78. Although not illustrated, it should be appreciated that thevalve seats and valve plungers fit around spring 70 and sit inside orare supported by cavity 78.

II. Fail Safe Pump and Valve Operation

Referring now to FIGS. 6 to 11, various embodiments for operating thepumps and valves described above in connection with assembly 10 andvalve/pump housing 20 are illustrated. FIGS. 1 to 5 illustrate anassembly 10, which includes a combination valve/pump housing 20 andadjoining plates 24, 26 and 30. The present invention is not howeverlimited to the this configuration. FIGS. 6 to 8 for example show threealternative configurations that each include alternative valve/pumphousings 120, 220 and 320, respectively. Each of the housings 120, 220and 320 define an aperture 80 through which piston 34 moves back andforth to pump fluid to and from a disposable cassette 90. Disposablecassette 90 is illustrated schematically in its operating position withrespect to the housings 120, 220 and 320. Disposable cassette 90 canhave various forms and in an embodiment includes a rigid portion (termincludes rigid and semi-rigid) 92 that defines a plurality of fluidpathways bounded also by upper and lower flexible membranes 94 and 96,respectively (which are sealed to rigid portion 92). One preferredmaterial for the flexible membranes 94 and 96 is discussed below inconnection with Section IV.

Housings 120, 220 and 320 each define a vacuum chamber 82 within which avacuum is applied to pull the lower flexible membrane or front sheet 96away from rigid portion 92 of cassette 90 when piston 34 and piston head36 are retracted inward towards the inside of the dialysis machine.FIGS. 6 to 8 each illustrate two pumps, however, the system of thepresent invention can have any number of pumps including one pump andmore than two pumps. FIGS. 6 to 8 show the left pump in a retractedposition, wherein dialysis fluid is pulled either from a supply (notillustrated) in a batch system, or from the patient (not illustrated),in a regeneration or CFPD type of dialysis system. With CFPD, the pumppulls dialysis fluid from the patient through one or more regenerationdevice, which contains materials that clean or regenerate the dialysate.

Various regeneration devices and materials are described in documentsSer. Nos. 10/623,317 and 10/624,150. Generally, any type of device thatutilizes any suitable amount and type of material to clean effectivelythe dialysate prior to reuse can be used. In an embodiment, the cleaningdevice includes a material that is capable of non-selective removal ofsolutes from the dialysate that have been removed from the patientduring therapy. The material can include any suitable sorbent material,such as carbon, activated carbon or other like material that iscontained within a suitable housing, such as a cartridge, in anyacceptable manner.

Other materials in addition to those which can non-selectively removesolutes from the dialysate can be used. The additional other materialsinclude, for example, materials that can selectively remove certainsolutes or the like from solution. In an embodiment, the additionalmaterials can include a binder or reactive sorbent material capable ofselectively removing urea, a binder or reactive sorbent material capableof selectively removing phosphate and/or the like. The use of materialscapable of selective removal of solutes, particularly urea, can enhancethe cleaning efficiency of the system so that the amount of dialysatenecessary for effective treatment is minimized.

The materials that can selectively remove solutes from solution, such asbinder materials, can include a variety of suitable and differentmaterials including, for example, polymeric materials that are capableof removing nitrogen-containing compounds, such as urea, creatinine,other like metabolic waste and/or the like in solution. In general,these types of materials contain a functional group(s) that chemicallybinds with urea or other like solutes. One type of material includesalkenylaromatic polymers containing phenylglyoxal that function tochemically bind urea. In general, the phenylglyoxal polymeric materialis made via acetylation performed in, for example, nitrobenzene followedby halogenation of the acetyl group and treatment withdimethylsulfoxide. Another example of a polymeric material that iscapable of selectively removing solutes, such as urea, from solutionincludes polymeric materials that contain a tricarbonyl functionalitycommonly known as ninhydrin. The present invention can include anysuitable type of material or combinations thereof to selectively removesolutes, such as urea, from solution as previously discussed.

One type of regeneration device is a cleaning cartridge. The cleaningcartridge can include a number of components in addition to the sorbentmaterials capable of removing solutes from the dialysate. For example,the cleaning cartridge may have the capability to remove all or aportion of electrolytes, such as sodium, potassium, or the like, fromthe dialysate solution. Here, an additional source of electrolytes insolution may be needed to replenish the dialysate after it has beencleaned. The cartridge may also be configured to release bicarbonate orthe like into the system depending on the type of sorbent material used.This can facilitate pH regulation of the dialysate. As necessary, thecartridge may be filtered to prevent proteins, particulate matter orlike constituents from leaching or exiting from the cartridge into thedialysate.

The cleaning cartridge is coupled to a dialysate loop via a cleaningfluid loop in an embodiment. The cartridge can include three separatelayers, such as a layer of carbon, a layer of a phosphate binder and alayer of a urea binder. The cleaning fluid path includes suitablecomponents to control the flow through the loop. In an embodiment, therate of flow of the dialysate through the cleaning fluid loop, e.g., thecleaning flow rate, is less than the flow through the main dialysisfluid loop.

In the illustrated embodiments, the vacuum communicates with membrane 96through chamber 82 of housings 120, 220 and 320. As discussed above inconnection with reference numeral 38 of FIG. 2, the vacuum is introducedin an embodiment into chamber 82 through a channel in piston 34 andpiston head 36. Piston head 36 in an embodiment defines grooves, such asgrooves forming a star shape extending from the vacuum channel 38orifice outwardly along the upper surface of piston head 36 to enablethe vacuum to spread more evenly between piston head 36 and lowerflexible membrane 96. The vacuum is alternatively introduced intochamber 82 via a separate fluid pathway (not illustrated) in housings120, 220 and 320 extending to a negative pressure source.

FIG. 6 illustrates one embodiment for actuating pump piston 34 andpiston head 36. Housing 120 defines a lower vacuum chamber 84 for eachof the pump assemblies in addition to upper vacuum chambers 82 describedabove. A spring 86 is placed inside vacuum chamber 84. The spring 86 iscoupled to a member 88, which is in turn coupled to piston 34. In analternative embodiment, member 88 and piston 34 are formed integrally.Member 88, piston 34 and piston head 36 can be of any suitable material,such as hard plastic or metal, for instance, aluminum, stainless steelor other non-corrosive material. Spring 86 pushes against a bottom ofhousing 120 and member 88 to force the piston 34 and piston head 36 tocontact lower flexible membrane 96 and push membrane 96 upward intorigid portion 92 of cassette 90. Spring 86 acts therefore to push ordispel fluid from disposable cassette 90.

To pump fluid into cassette 90, a deep vacuum is applied to chamber 84,which compresses spring 86. The spring in turn pulls member 88 andretracts piston 34 and piston head 36. The deep vacuum applied tochamber 34 is strong enough to overcome the spring constant andcompression force of spring 86. In an embodiment, the deep vacuumapplied to chamber 84 is from about −5 to about −30 psig.

When the deep vacuum is applied to chamber 84, a shallow vacuum isapplied to chamber 82 simultaneously to pull lower flexible membrane 96against the retracting piston head 36. The shallow vacuum is between 0and −10 psig. In one embodiment a rolling diaphragm 98 is providedbetween member 88 and an inner wall of vacuum chamber 84. The diaphragm98 seals to member 88 and the inner wall and separates the vacuumsapplied to chamber 82 and chamber 84. The back and forth movement ofmember 88, piston 34 and piston head 36 due to the expansion andretraction of spring 86 and the alternating application of a deep vacuumand a shallow vacuum to chamber 84 guides the rolling diaphragm 98 sothat a nearly frictionless linear movement is generated.

When the deep vacuum 84 is removed so that spring 86 begins to expand,it is possible that due to the movement of the piston assembly or to acontinuing shallow vacuum in chamber 82, rolling diaphragm 98 willinvert from the generally downwardly extending orientation shown in FIG.6. To prevent this from happening, a shallow vacuum is applied inchamber 84 during the push fluid stroke. The shallow vacuum in chamber84 is also between 0 and −10 psig. in one embodiment. The shallow vacuumin an embodiment is the same shallow vacuum applied to chamber 82 sothat the forces on either side of the diaphragm 98 via the shallowvacuums cancel one another. The shallow vacuum in chamber 84 is notlarge enough to overcome the spring constant of spring 86. Spring 86 issized to apply the appropriate amount of force via piston head 36 to thelower flexible membrane 96, which can be as high as 35 lbs., taking intoaccount that a negative force via the shallow vacuum in chamber 84 isacting against spring 86 during the pump out or dispel stroke.

FIGS. 6 to 8 illustrate one preferred sequence for operating multiplepumps. Pump pistons 34 move in and out alternatively, filling andemptying associated pump fluid chambers defined between rigid portion 92and lower flexible membrane 96. The alternating pumps create a virtuallyconstant flow of fluid to the patient. Dialysate intake and exhaustvalves defined in part by disposable cassette 90 are opened and closedin conjunction with the movement of the pump pistons 34. In anembodiment, an intake valve (not illustrated) is open as an associatedpump piston 34 retracts. The intake valve closes when the pump piston 34extends towards cassette 90. The dialysis cassette also defines anexhaust valve that is closed as the associated pump piston retracts. Theexhaust valve opens as the pump piston extends into cassette 90.

FIG. 7 illustrates an alternative pump actuator housed inside housing220. The shallow vacuum is again applied to chamber 82, for example, viaan orifice in pump piston 34 and piston head 36. The shallow vacuumdraws the lower flexible membrane 96 up against pump piston heads 36. Asin any of the embodiments described herein, the shallow vacuum withinchamber 82 can be maintained or not maintained when pump piston 34extends toward cassette 90 to dispel fluid from cassette 90. In FIG. 7,the member 88 and rolling diaphragm 98 of FIG. 6 are replaced by acylinder 102 defining a deep vacuum chamber 104. A piston rod 106attaches to piston 34 and seals against an inner surface of cylinder 102via seals 108. A shaft seal, which can be of any known type, hereafterreferred to as o-ring 112 is also placed within housing 220 betweenshaft opening 80 and the piston 34 to maintain the vacuum within chamber82.

The operation of the cylinder 102 and cylinder rod 106 in conjunctionwith piston 34 is substantially the same as described above withdiaphragm 98 and spring 86 of FIG. 6. In FIG. 7, a spring 114 isprovided within each cylinder 102. The spring 114 pushes againstcylinder rod 106, which in turn pushes piston 34 and piston head 36towards rigid cassette 90. In an alternative embodiment, piston rod 106can be eliminated, wherein piston 34 seals directly to the inner surfaceof cylinder 102, and wherein spring 114 is sized to push directlyagainst piston 34. To withdraw the piston 34, a deep vacuum is appliedto chamber 104 within cylinder 102, which overcomes the spring constantand compression resistance of spring 114.

Because the rolling diaphragm is not used, a shallow vacuum need not bemaintained within chamber 104 in connection with the pump-out or fluiddispelling stroke. A shallow vacuum may be maintained within chamber 82as described above, however, upon the pump-out or fluid dispellingstroke. Spring 114 does not need to overcome a residual negativepressure as in the case with embodiment of FIG. 6. Spring 114 maytherefore be of a slightly decreased strength with respect to spring 86and the deep vacuum may accordingly be slightly less than the deepvacuum employed with FIG. 6.

In an alternative embodiment, a positive pressure is applied outside ofcylinder 102 to push rod 106 and compress spring 114 as opposed todrawing a vacuum within chamber 104 of cylinder 102. The o-ring seal 112is still required to separate the positive pressure outside of cylinder102 from the vacuum introduced into chamber 82. When the positivepressure is relieved, spring 114 pushes rod 106 and piston 34 asdescribed above.

Referring now to FIG. 8, a further alternative embodiment eliminates thedeep vacuum altogether and instead uses an electrically operated linearor rotary/linear actuator 32. Actuator 32 is also illustrated above inconnection with FIG. 1. Linear actuator 32 in an embodiment is a linearstepper motor, a rotary stepper motor coupled to a lead or ball screw, arotary servo motor coupled to a lead or ball screw or other type ofelectrically, pneumatically or hydraulically operated linear actuator.Pump actuator 32 couples in an embodiment directly to piston 34 via acoupler 116, which in an embodiment allows for slight misalignmentbetween piston 34 and an output shaft of pump actuator 32. Pump actuator32 eliminates altogether the need for the vacuum chamber 84, the deepvacuum and the residual shallow vacuum. A shallow vacuum is stillrequired in chamber 82 to pull lower flexible membrane 96 away fromrigid portion 92 when piston head 36 retracts away from cassette 90.O-ring 112 is provided between opening 80 in housing 320 and shaft 34 toform in part the enclosed vacuum chamber 82.

Referring now to FIG. 9, a further alternative embodiment for a pumpactuator is illustrated. A portion of a housing 420 is illustrated.Housing 420 includes many of the same components as housing 120, such asthe a shallow vacuum chamber 82, the deep vacuum chamber 84, the spring86 and the rolling diaphragm 98 that couples sealingly to member 88(connected to piston 34) and an inner surface of housing 420 (definingdeep chamber 84). These components operate as described above, wherein ashallow vacuum is applied to chamber 82 to pull lower flexible membrane96 away from rigid portion 92 of cassette 90. A deep vacuum is appliedto chamber 84 to compress spring 86, which is coupled to member 88 andpiston 34. Compression of spring 86 pulls piston 34 away from cassette90. When the deep vacuum is removed from chamber 84, spring 86decompresses and pushes piston 34 and piston head 36 towards cassette 90to dispel fluid that exists between flexible member 96 and rigid portion92.

The embodiment of FIG. 9 includes an additional rolling diaphragm 118.Each of the rolling diaphragms 98 and 118 is made of a strong, airimpermeable and flexible material, such as silicone rubber sheeting orfabric reinforced silicone rubber. The additional rolling diaphragm 118connects sealingly to an additional member 124 coupled to piston 34 andalso sealingly to an inner surface of housing 420.

The combination of rolling diaphragms 98 and 118 creates a third sealedchamber 122 between chambers 82 and 84. The shallow vacuum in chamber 82does not have the ability to corrupt the operation of diaphragm 98 aswith the embodiment in FIG. 6. A separate shallow vacuum does nottherefore need to be maintained in chamber 84 upon the fluid push ordispelling stroke. The spring constant 86 does not need to be chosen toovercome additionally the shallow vacuum in chamber 84. Because thespring 86 can be smaller, the level of deep vacuum in chamber 84 canlikewise be decreased.

A number of options exists for controlling the pressure within thirdchamber 122. The pressure within third chamber 122 can be either beatmospheric or positive. If atmospheric, the negative pressuremaintained within chambers 82 and 84 maintains the rolling diaphragms118 and 98, respectively, in the proper illustrated orientations. Apositive pressure applied to chamber 122 acts additionally to compressspring 86, push diaphragms 98 and 118 into their proper orientation, andmay be used to withdraw piston 34 from cassette 90 during the fillstroke in place of or in addition to the deep vacuum maintained inchamber 84 to overcome the force of spring 86.

Referring now to FIGS. 10 and 11, an embodiment for actuating the valveplungers 42 illustrated above in FIG. 2 is illustrated. As also seen inFIG. 5, a plunger spring 70 operates to push plunger 42 towards one ofthe flexible membranes 94 or 96 of an alternative disposable cassette190. Flexible membranes 94 and 96 seal to a semi-rigid or rigid, i.e.,plastic, portion 192. In the embodiments described in connection withFIGS. 1 to 5, plunger spring 70 is housed within valve/pump housing 20,intermediate sheets 24 and 26 and front plate 30. In the alternativeembodiment illustrated in FIG. 10, plunger spring 70 and plunger 42 arehoused within a valve housing 130.

Valve housing 130 as with any of the pump housings 120, 220, 320 and420, can be of a suitable hard plastic or be metal, such as a lightmetal, for example, aluminum. Valve housing 130 includes an outersection 132 and an inner section 134. A diaphragm 136 is sealed betweenouter section 132 and inner section 134. Diaphragm 136 in an embodimentis of the same material described above for rolling diaphragms 98 and118 and is strong, flexible and air impermeable in one preferredembodiment. The plungers 42 connect to their respective diaphragms 136via members 138. In the illustrated embodiment, diaphragms 136 aresecured to members 138 via attachment mechanisms, such as bolts. Plungerspring 70 pushes against member 138, moving member 138 and plunger 42.

In an embodiment a compliant material 142 is placed at the end of thevalve plunger 42 facing the respective flexible membrane 94 and 96. Thecompliant material can be rubber, for example, silicone rubber, neoprenerubber, Viton or ethylene propylene dienemethylene (“EPDM”). Thecompliant material aids in creating an airtight seal between valveplunger 42 and flexible sheet 94 or 96, compensating for minor surfaceimperfections in membranes 94 and 96 and/or in the rigid portion of 192of cassette 190. The surface of rigid portion 192 that contacts andseals to the flexible membranes 94 and 96 is smooth in an embodiment oralternatively contains one or more concentric sealing rings which: (i)prevents the sheeting from adhering to rigid portion 192 when the valveis commanded to open; and (ii) provides multiple seals, dividingeffectively the fluid pressure within cassette 190 that must be overcomeby a factor of two or three, etc.

Similar to the operation of the pump in connection with FIG. 6, a deepvacuum is applied to chamber 144 defined by section 132 of housing 130,diaphragm 136 and member 138. A shallow vacuum is applied to chamber146, which is defined by section 134 of housing 130, diaphragm 136 andmember 138. The shallow vacuum applied within chamber 146 acts to pullthe sheet 94, 96 against plunger 142 to open a fluid passageway 148 asillustrated by FIG. 11. Fluid passage 148 allows dialysis fluid to flowfrom passageway 152 defined by rigid portion 192 to passageway 154defined by rigid portion 192 as illustrated by the arrow in FIG. 11.

To open fluid passageway 148, a deep vacuum is applied within chamber144. Simultaneously, a shallow vacuum is applied within chamber 146. Thedeep vacuum is strong enough to overcome the force provided by plungerspring 70, e.g., two to ten lbs., as well as a counteracting forceapplied to diaphragm 136 via the shallow vacuum within chamber 146. Inan embodiment, plunger spring 70 and plunger 42 apply a force of betweenzero and about 35 psig. to seal the membrane against pumping pressures,which can range from one to over 10 psig., providing a safety factor ofthree to one. FIG. 10 also illustrates that it is possible to havevalves operate on multiple sides of cassette 190. Although notillustrated, it should be appreciated that multiple pumps can operatewith multiple sides of the cassette 190 as well.

To close fluid passageway 148, the deep vacuum is removed within chamber144. The shallow vacuum applied within chamber 146 may or may not bemaintained. Spring 70 pushes plunger 42 against membrane 94, 96, whichin turn seals against rigid portion 192. Spring 70 is between 0.5 and1.25 inches when compressed and 0.75 to 1.5 inches in free length. Thespring rates can range from about 5 to about 10.

III. Cassette Auto Alignment Feature

Referring now to FIGS. 12 to 14, an apparatus and method forautomatically aligning the disposable cassette within a dialysis machineis illustrated. The apparatus and method also detect whether a cassettemisalignment problem or a cassette integrity problem exists. FIG. 12illustrates a dialysis machine 100 and a disposable cassette 150,wherein the cassette 150 is about to be loaded into machine 100.Cassette 150, like the cassettes described above, includes a rigid,e.g., plastic portion 162, an upper flexible membrane 94 and a lowerflexible membrane 96. Rigid portion 162 and lower flexible membrane 96define three pump chambers 168, 172 and 174. As discussed above, each ofthe embodiments of the present invention can have one or more pumpchambers.

The dialysis machine 100 includes a housing having a base 170 and lid180, which in the illustrated embodiment, is hinged to base 170 so as toform a clamshell-like structure. In the illustrated embodiment, assembly10 of FIGS. 1 to 5 is housed inside of base 170. Front plate 30 ofassembly 10 faces outward and is positioned to abut against and operatewith cassette 150. As described above, pump piston heads 36 extendthrough front plate 30. For reference, valve plungers 42 and sensors 74are also illustrated. For further reference, machine 100 is shown havinga screen 176 with various indicia 178 shown thereon.

To control the dialysis therapy, a number of input devices 184 areprovided, such as buttons, knobs and other types of switches.Alternatively, screen 176 is operable with a touch screen and a touchscreen controller that allows an operator or patient to control thedialysis therapy through input devices displayed on screen 176. Acontroller (not illustrated), which can include multiple processors,such as a supervisory processor and a plurality of delegate processors:(i) controls screen 176; (ii) accepts inputs from devices 184; (iii)accepts inputs from sensors 74; and (iv) controls the actuation of thepistons 34, piston heads 36 and valve plungers 42, as well as otherfunctions.

An inflatable bladder 182 is provided to inflate and lock cassette 150against front plate 30 when the cassette 150 is in position. In theillustrated embodiment, inflatable bladder 182 is located on an innersurface 186 of lid 180. After cassette 150 is placed against front plate30, lid 180 is closed. The controller then commands a pressure source toinflate inflatable bladder 182 to lock cassette 150 in place. Prior tothe inflation of bladder 182, it is possible for cassette 150 to moveslightly between front plate 30 and inner surface 186 of lid 180. It isalso possible that either: (i) cassette 150 is misaligned with respectto front plate 30 when placed inside machine 100; and/or (ii) anintegrity problem, e.g., a leak, exists between one of the flexiblemembranes 94, 96 and rigid portion 162.

FIGS. 13 and 14 illustrate a cross section taken through lines XIII-XIIIand XIV-XIV respectively, of FIG. 12 after cassette 150 has been loadedinto machine 100 and before inflatable bladder 182 has been inflated. Asection of lid 180, which is hollow in an embodiment, is illustrated inthe closed position residing directly above cassette 150. The lid islocked mechanically in an embodiment before the bladder 182 inflates,the pumps activate, etc. Inflatable bladder 182 loosely contacts upperflexible membrane 94. It should be appreciated that the cassette 150 canbe loaded vertically in an alternative embodiment. Front plate 30 wouldthen be disposed vertically inside base 170.

FIG. 13 illustrates that a slight misalignment exists between the pumpchambers and piston heads. Pump chambers 168, 172 and 174 of cassette150 are slightly to the right of the proper position above piston heads36. Cassette 150 is slightly misaligned therefore to the right. In thedialysis therapy startup sequence of the present invention, thecontroller (not illustrated) commands at least one and in one preferredembodiment all of the pump pistons 34 and associated piston heads 36 tomove upwards (or laterally for side load) to the fluid dischargeposition. FIG. 13 includes arrows illustrating this upward movement.

FIG. 14 shows an arrow pointing to the left indicating that as thepiston heads 36 move upward, the heads contact lower flexible membrane96 and abut rigid portion 162, causing the cassette 150 to slide to theleft and move into the proper operating position. As illustrated, pistonheads 36 and fluid pump chambers 168, 172 and 174 are tapered at theirrespective ends, which aids in aligning cassette 150 with respect frontplate 30. The provision of at least two pump pistons ensures alignmentin two dimensions. In an alternative embodiment pump pistons 34 can beslightly misaligned with respect to one another so as to provide anoffset in both horizontal dimensions. If cassette 150 and front plate 30are disposed vertically, multiple pump pistons 34 provide alignment inmultiple vertical dimensions.

The cassette 150 may be misaligned to the point that piston heads 36 aretoo far out of alignment with respect to fluid pumping chambers 168, 172and 174 for the misalignment to be corrected automatically. One or moresensors 188, such as strain gauge sensors, are provided to sense aresistance to the movement of the pump piston 34 and piston head 36. Ifthe cassette 150 does not move into alignment, the force applied bypistons 134 to the rigid portion 162 of the cassette 150 is transferredacross rigid portion 162 and is sensed by strain gauge 188. Strain gauge188 sends an input to the controller. The controller is programmed towithdraw the pump pistons 34 and send an error message to screen 176 ifthe strain gauge input increases to an alarm set-point level.

It is also possible that due to improper formation of the rigid portion162, or improper placement of flexible membrane 96 onto rigid portion162, that the movement of one or more of the pistons 34 may be impeded.In such a case, as before, a force is transferred by the impeded piston,through the rigid portion 162, to the force sensor 188. Once again,sensor 188 sends a signal to the controller, which sends an alarmmessage to screen 176. In an embodiment, the alarm message alerts theuser to the fact that the cassette could be misaligned or have anintegrity problem. In an alternative environment, such as when multiplesensors 188 are provided, it may be possible for the controller todetermine whether the problem is misalignment or integrity and send theproper corresponding message to screen 176. In either case, thecontroller halts the upward movement of the pump piston(s) and canretract same to alleviate the associated stress.

Once cassette 150 is determined to be in the proper position, asillustrated in connection with FIG. 14, the controller commands apressure source to inflate inflatable bladder 182, locking cassette 150between lid 180 and front plate 30. Either at this time, prior to thistime or after this time, one or more of the pump pistons 34 can retractif needed.

IV. Flexible Membrane Material

The pumping membrane film referred to herein with reference numerals 94and 96 preferably is fabricated from a non-PVC containing, thermoplasticpolymeric material and can be of a monolayer structure as shown in FIG.15 or a multiple layer structure as shown in FIG. 16. The film can befabricated using standard thermoplastic processing techniques such asextrusion, coextrusion, extrusion lamination, lamination, blownextrusion, tubular extrusion, cast extrusion or coextrusion, compressionmolding and thermoforming. Thermoforming is one preferred method forfabricating the film as it is well suited for fabricating the filmhaving an elongation from about 5% to 40% and more preferably from 10%to 30%, and most preferably from 20 to 25%. In a preferred form of theinvention, a portion of the film and more preferably a central portionwill be domed. In a more preferred form of the invention the dome willhave a diameter of 1.60 inches and a depth of 0.26 inches. The film willhave a thickness of less than 15 mils and more preferably less than 12mils and more preferably from about 11 mils to about 4 mils.

In a preferred form of the invention, the film should satisfy certainphysical property requirements to function as a pumping membrane asdescribed herein. The film should have a mechanical modulus to achieveprecise fluid volume delivery rates. In a preferred form of theinvention the modulus of elasticity will be less than 20,000 psi, morepreferably less than 15,000 psi and even more preferably less than10,000 psi when measured in accordance with ASTM D-882. The modulus ofelasticity should remain essentially constant over a temperature rangeof from 5 to 40° C.

The pumping membrane film should also be sufficiently compatible withthe material of the cassette 92, 150 and 192 so that the membrane filmcan be permanently adhered to the cassette using standard sealingtechniques such as thermal welding, sonic welding or solvent bonding.Most preferably the film is attached to the cassette by heat sealing.

The pumping membrane film should be capable of being deformed by thepiston head 36 or valve plungers 42 for ten thousand pumping strokeswithout a significant change in the volume of fluid being delivered. Thevolume will not vary by more than about 15 percent, more preferablyabout 10 percent and most preferably about 5 percent after 10,000pumping strokes or after a therapy session or the like.

The film should also show minimal variation in mechanical propertiesover operating temperatures of from 5 to 40° C. In a preferred form ofthe invention the film can withstand contact with a 75° C. surfaceheater and withstand a spot temperature of 95° C. for 1 to 3 seconds. Inyet another preferred form of the invention the film can have a heattransfer coefficient of greater than 0.20 Watts/Minute-Kelvin (K) for afilm having a thickness of 5 mils.

In yet another preferred form of the invention a surface of the filmfacing the piston head 36 or valve plungers 42 will not stick to thesedevices to the extent it interrupts the pumping operation. In onepreferred form of the invention, the film will have a textured surfaceto assist in preventing sticking of these devices to the film. Thetextured surface can include a matte or taffeta finish or other surfacemodification to reduce the surface area of the outer surface of the filmthe piston head 36 or valve plungers 42 contacts. The surface texturecan be embossed or otherwise imparted to the film using techniques wellknown to the skilled artisan in the field of polymeric film processing.

The film, in a preferred form of the invention, will have a minimum orbe free of gels. Gels are a heterogeneity in the film that appears as alocal thickness increase. Gels are undesirable as they are moresusceptible than other portions of the film to forming leaks.

It is also preferred the film not readily or permanently stick to itselfso that the film can be fabricated, stored and assembled into thedevices described herein with a minimum of challenges well known tothose skilled in the art that result from a film sticking to itself.

It is also desirable the film present a barrier to water vaportransmission so that a minimum or insignificant amount of water is lostthrough the film during an eight hour therapy session. In a preferredform of the invention the water vapor transmission rate (WVTR) of thefilm when measured at 37.8° C. at 100% relative humidity is less thanabout 0.500 g/100 in²/day and more preferably less than 0.300 g/100in²/day. Also, in a preferred form of the invention, the WVTR whenmeasured at 25° C. at 100% relative humidity will be less than 0.200g/100 in²/day and more preferably less than 0.150 g/100 in²/day.

The film should also be resistant to tearing and cutting. The filmshould resist tearing when an unsupported portion of the film isimpinged upon by a plunger having a diameter of 1.6 inches with a5-pound force applied thereto. In another preferred form of theinvention, the film has an Elmendorf tear strength when measured inaccordance with ASTM D 1922 of from 300 to 3,000 g, more preferably from500-1,000 g. The film, in a preferred form of the invention, should havea durometer from about 45 to about 65 Shore A.

The film, in a preferred form of the invention, is capable of beingsterilized by gamma or ethylene oxide sterilization techniques.

Again, in a preferred form of the invention, the film will have hightransparency such as an optical haze of less than 30%, and morepreferably less than 15% and even more preferably less than 10% and mostpreferably less than 5%, when measured for a film 9 mils thick and inaccordance to ASTM D-1003.

Suitable non-PVC containing polymers include polyolefins, ethylene andlower alkyl acrylate copolymers, ethylene and lower alkyl substitutedalkyl acrylate copolymers, ethylene vinyl acetate copolymers,polybutadienes, polyesters, polyamides, and styrene and hydrocarboncopolymers.

Suitable polyolefins include homopolymers and copolymers obtained bypolymerizing alpha-olefins containing from 2 to 20 carbon atoms, andmore preferably from 2 to 10 carbons. Therefore, suitable polyolefinsinclude polymers and copolymers of propylene, ethylene, butene-1,pentene-1,4-methyl-1-pentene, hexene-1, heptene-1, octene-1, nonene-1and decene-1. Most preferably the polyolefin is a homopolymer orcopolymer of propylene or a homopolymer or copolymer of polyethylene.

Suitable homopolymers of polypropylene can have a stereochemistry ofamorphous, isotactic, syndiotactic, atactic, hemiisotactic orstereoblock. In one preferred form of the invention the homopolymer ofpolypropylene is obtained using a single site catalyst.

Suitable copolymers of propylene are obtained by polymerizing apropylene monomer with an α-olefin having from 2 to 20 carbons. In amore preferred form of the invention the propylene is copolymerized withethylene in an amount by weight from about 1% to about 20%, morepreferably from about 1% to about 10% and most preferably from 2% toabout 5% by weight of the copolymer. The propylene and ethylenecopolymers may be random or block copolymers. In a preferred form of theinvention, the propylene copolymer is obtained using a single-sitecatalyst.

It is also possible to use a blend of polypropylene and α-olefincopolymers wherein the propylene copolymers can vary by the number ofcarbons in the α-olefin. For example, the present invention contemplatesblends of propylene and α-olefin copolymers wherein one copolymer has a2 carbon α-olefin and another copolymer has a 4 carbon α-olefin. It isalso possible to use any combination of α-olefins from 2 to 20 carbonsand more preferably from 2 to 8 carbons. Accordingly, the presentinvention contemplates blends of propylene and α-olefin copolymerswherein a first and second α-olefins have the following combination ofcarbon numbers: 2 and 6, 2 and 8, 4 and 6, 4 and 8. It is alsocontemplated using more than 2 polypropylene and α-olefin copolymers inthe blend. Suitable polymers can be obtained using a catalloy procedure.

It may also be desirable to use a high melt strength polypropylene. Highmelt strength polypropylenes can be a homopolymer or copolymer ofpolypropylene having a melt flow index within the range of 10 grams/10min to 800 grams/10 min., more preferably 30 grams/10 min. to 200grams/10 min, or any range or combination of ranges therein. High meltstrength polypropylenes are known to have free-end long chain branchesof propylene units. Methods of preparing polypropylenes which exhibit ahigh melt strength characteristic have been described in U.S. Pat. Nos.4,916,198; 5,047,485; and 5,605,936 which are incorporated herein byreference and made a part hereof. One such method includes irradiating alinear propylene polymer in an environment in which the active oxygenconcentration is about 15% by volume with high energy ionization energyradiation at a dose of 1 to 10⁴ megarads per minute for a period of timesufficient for a substantial amount of chain scission of the linearpropylene polymer to occur but insufficient to cause the material tobecome gelatinous. The irradiation results in chain scission. Thesubsequent recombination of chain fragments results in the formation ofnew chains, as well as joining chain fragments to chains to formbranches. This results in the desired free-end long chain branched, highmolecular weight, non-linear, propylene polymer material. Radiation ismaintained until a significant amount of long chain branches form. Thematerial is then treated to deactivate substantially all the freeradicals present in the irradiated material.

High melt strength polypropylenes can also be obtained as described inU.S. Pat. No. 5,416,169, which is incorporated in its entirety herein byreference and made a part hereof, when a specified organic peroxide(di-2-ethylhexyl peroxydicarbonate) is reacted with a polypropyleneunder specified conditions, followed by melt-kneading. Suchpolypropylenes are linear, crystalline polypropylenes having a branchingcoefficient of substantially 1, and, therefore, have no free endlong-chain branching and will have a intrinsic viscosity of from about2.5 dl/g to 10 dl/g.

Suitable homopolymers of ethylene include those having a density ofgreater than 0.915 g/cc and includes low density polyethylene (LDPE),medium density polyethylene (MDPE) and high density polyethylene (HDPE).

Suitable copolymers of ethylene are obtained by polymerizing ethylenemonomers with an α-olefin having from 3 to 20 carbons, more preferably3-10 carbons and most preferably from 4 to 8 carbons. It is alsodesirable for the copolymers of ethylene to have a density as measuredby ASTM D-792 of less than about 0.915 g/cc and more preferably lessthan about 0.910 g/cc and even more preferably less than about 0.905g/cc. Such polymers are often times referred to as VLDPE (very lowdensity polyethylene) or ULDPE (ultra low density polyethylene).Preferably the ethylene α-olefin copolymers are produced using a singlesite catalyst and even more preferably a metallocene catalyst systems.Single site catalysts are believed to have a single, sterically andelectronically equivalent catalyst position as opposed to theZiegler-Natta type catalysts which are known to have a mixture ofcatalysts sites. Such single-site catalyzed ethylene α-olefins are soldby Dow under the trade name AFFINITY, DuPont Dow under the trademarkENGAGE® and by Exxon under the trade name EXACT. These copolymers shallsometimes be referred to herein as m-ULDPE.

Suitable copolymers of ethylene also include ethylene and lower alkylacrylate copolymers, ethylene and lower alkyl substituted alkyl acrylatecopolymers and ethylene vinyl acetate copolymers having a vinyl acetatecontent of from about 8% to about 40% by weight of the copolymer. Theterm “lower alkyl acrylates” refers to comonomers having the formula setforth in Diagram 1:

The R group refers to alkyls having from 1 to 17 carbons. Thus, the term“lower alkyl acrylates” includes but is not limited to methyl acrylate,ethyl acrylate, butyl acrylate and the like.

The term “alkyl substituted alkyl acrylates” refers to comonomers havingthe formula set forth in Diagram 2:

R₁ and R₂ are alkyls having 1 to 17 carbons and can have the same numberof carbons or have a different number of carbons. Thus, the term “alkylsubstituted alkyl acrylates” includes but is not limited to methylmethacrylate, ethyl methacrylate, methyl ethacrylate, ethyl ethacrylate,butyl methacrylate, butyl ethacrylate and the like.

Suitable polybutadienes include the 1,2- and 1,4-addition products of1,3-butadiene (these shall collectively be referred to aspolybutadienes). In a more preferred form of the invention the polymeris a 1,2-addition product of 1,3 butadiene (these shall be referred toas 1,2 polybutadienes). In an even more preferred form of the inventionthe polymer of interest is a syndiotactic 1,2-polybutadiene and evenmore preferably a low crystallinity, syndiotactic 1,2 polybutadiene. Ina preferred form of the invention the low crystallinity, syndiotactic1,2 polybutadiene will have a crystallinity less than 50%, morepreferably less than about 45%, even more preferably less than about40%, even more preferably the crystallinity will be from about 13% toabout 40%, and most preferably from about 15% to about 30%. In apreferred form of the invention the low crystallinity, syndiotactic 1,2polybutadiene will have a melting point temperature measured inaccordance with ASTM D 3418 from about 70° C. to about 120° C. Suitableresins include those sold by JSR (Japan Synthetic Rubber) under thegrade designations: JSR RB 810, JSR RB 820, and JSR RB 830.

Suitable polyesters include polycondensation products of di- orpolycarboxylic acids and di or poly hydroxy alcohols or alkylene oxides.In a preferred form of the invention the polyester is a polyester ether.Suitable polyester ethers are obtained from reacting 1,4 cyclohexanedimethanol, 1,4 cyclohexane dicarboxylic acid and polytetramethyleneglycol ether and shall be referred to generally as PCCE. Suitable PCCE'sare sold by Eastman under the trade name ECDEL. Suitable polyestersfurther include polyester elastomers which are block copolymers of ahard crystalline segment of polybutylene terephthalate and a secondsegment of a soft (amorphous) polyether glycols. Such polyesterelastomers are sold by Du Pont Chemical Company under the trade nameHYTREL®.

Suitable polyamides include those that result from a ring-openingreaction of lactams having from 4 to 12 carbons. This group ofpolyamides therefore includes nylon 6, nylon 10 and nylon 12. Acceptablepolyamides also include aliphatic polyamides resulting from thecondensation reaction of di-amines having a carbon number within a rangeof 2 to 13, aliphatic polyamides resulting from a condensation reactionof di-acids having a carbon number within a range of 2 to 13, polyamidesresulting from the condensation reaction of dimer fatty acids, and amidecontaining copolymers. Thus, suitable aliphatic polyamides include, forexample, nylon 66, nylon 6,10 and dimer fatty acid polyamides.

The styrene of the styrene and hydrocarbon copolymer includes styreneand the various substituted styrenes including alkyl substituted styreneand halogen substituted styrene. The alkyl group can contain from 1 toabout 6 carbon atoms. Specific examples of substituted styrenes includealpha-methylstyrene, beta-methylstyrene, vinyltoluene, 3-methylstyrene,4-methylstyrene, 4-isopropylstyrene, 2,4-dimethylstyrene,o-chlorostyrene, p-chlorostyrene, o-bromostyrene,2-chloro-4-methylstyrene, etc. Styrene is the most preferred.

The hydrocarbon portion of the styrene and hydrocarbon copolymerincludes conjugated dienes. Conjugated dienes which may be utilized arethose containing from 4 to about 10 carbon atoms and more generally,from 4 to 6 carbon atoms. Examples include 1,3-butadiene,2-methyl-1,3-butadiene (isoprene), 2,3-dimethyl-1,3-butadiene,chloroprene, 1,3-pentadiene, 1,3-hexadiene, etc. Mixtures of theseconjugated dienes also may be used such as mixtures of butadiene andisoprene. The preferred conjugated dienes are isoprene and1,3-butadiene.

The styrene and hydrocarbon copolymers can be block copolymers includingdi-block, tri-block, multi-block, and star block. Specific examples ofdiblock copolymers include styrene-butadiene, styrene-isoprene, and thehydrogenated derivatives thereof. Examples of triblock polymers includestyrene-butadiene-styrene, styrene-isoprene-styrene,alpha-methylstyrene-butadiene-alpha-methylstyrene, andalpha-methylstyrene-isoprene-alpha-methylstyrene and hydrogenatedderivatives thereof.

The selective hydrogenation of the above block copolymers may be carriedout by a variety of well known processes including hydrogenation in thepresence of such catalysts as Raney nickel, noble metals such asplatinum, palladium, etc., and soluble transition metal catalysts.Suitable hydrogenation processes which can be used are those wherein thediene-containing polymer or copolymer is dissolved in an inerthydrocarbon diluent such as cyclohexane and hydrogenated by reactionwith hydrogen in the presence of a soluble hydrogenation catalyst. Suchprocedures are described in U.S. Pat. Nos. 3,113,986 and 4,226,952, thedisclosures of which are incorporated herein by reference and made apart hereof.

Particularly useful hydrogenated block copolymers are the hydrogenatedblock copolymers of styrene-isoprene-styrene, such as astyrene-(ethylene/propylene)-styrene block polymer. When apolystyrene-polybutadiene-polystyrene block copolymer is hydrogenated,the resulting product resembles a regular copolymer block of ethyleneand 1-butene (EB). As noted above, when the conjugated diene employed isisoprene, the resulting hydrogenated product resembles a regularcopolymer block of ethylene and propylene (EP). One example of acommercially available selectively hydrogenated block copolymer isKRATON G-1652 which is a hydrogenated SBS triblock comprising 30%styrene end blocks and a midblock equivalent is a copolymer of ethyleneand 1-butene (EB). This hydrogenated block copolymer is often referredto as SEBS. Other suitable SEBS or SIS copolymers are sold by Kurrarryunder the tradename SEPTON® and HYBRAR®.

It may also be desirable to use graft modified styrene and hydrocarbonblock copolymers by grafting an alpha,beta-unsaturated monocarboxylic ordicarboxylic acid reagent onto the selectively hydrogenated blockcopolymers described above.

The block copolymers of the conjugated diene and the vinyl aromaticcompound are grafted with an alpha,beta-unsaturated monocarboxylic ordicarboxylic acid reagent. The carboxylic acid reagents includecarboxylic acids per se and their functional derivatives such asanhydrides, imides, metal salts, esters, etc., which are capable ofbeing grafted onto the selectively hydrogenated block copolymer. Thegrafted polymer will usually contain from about 0.1 to about 20%, andpreferably from about 0.1 to about 10% by weight based on the totalweight of the block copolymer and the carboxylic acid reagent of thegrafted carboxylic acid. Specific examples of useful monobasiccarboxylic acids include acrylic acid, methacrylic acid, cinnamic acid,crotonic acid, acrylic anhydride, sodium acrylate, calcium acrylate andmagnesium acrylate, etc. Examples of dicarboxylic acids and usefulderivatives thereof include maleic acid, maleic anhydride, fumaric acid,mesaconic acid, itaconic acid, citraconic acid, itaconic anhydride,citraconic anhydride, monomethyl maleate, monosodium maleate, etc.

The styrene and hydrocarbon block copolymer can be modified with an oilsuch as the oil modified SEBS sold by the Shell Chemical Company underthe product designation KRATON G2705.

In a most preferred form of the invention the membrane film will be amonolayer structure as shown in FIG. 15 and be fabricated from a m-ULDPEresin. For multiple layer films having two layers as shown in FIG. 16 ormore it is desirable for an inner, solution contacting layer to be am-ULDPE and the layer or layers outward therefrom (outer layer) can be apolymeric material selected from a polymer set forth above, a metal foilor paper. The pumping film is attached to the cassette and has a portionattached to the cassette and another portion unsupported by the cassetteand extends between supported portions of the cassette. The film isgenerally taught between the portions where the film attaches to thecassette. Thus, the film extends between a first support and a secondsupport and satisfies one or more of the physical properties set forthabove. The pumping film overlies a fluid reservoir and is moveable froma first position to a second position to move fluid through thereservoir. The film is moved between the first and second position inresponse to a single or a series of periodic impingements of the film bythe piston head 36 or valve plungers 42 or the like on a portion of thefilm not supported. While the cassette shown herein is generallyrectangular shaped, it could have numerous different shapes such aspolygonal, round, elliptical and irregular shaped without departing fromthe scope of the invention.

The cassette is preferably fabricated from a thermoplastic polymer andmore preferably from a rigid thermoplastic polymer. In a preferred formof the invention the cassette is fabricated from a polyolefin such as ahomopolymer or copolymer of propylene as described above or ahomopolymer or copolymer of a cyclic olefin or a homopolymer orcopolymer of a bridged polycyclic hydrocarbon. Such polymers shallsometimes be collectively referred to as COCs.

Suitable homopolymer and copolymers of cyclic olefins and bridgedpolycyclic hydrocarbons and blends thereof can be found in U.S. Pat.Nos. 5,218,049; 5,854,349; 5,863,986; 5,795,945; 5,792,824; 4,993,164;5,008,356; 5,003,019; and 5,288,560 all of which are incorporated intheir entirety herein by reference and made a part hereof. In apreferred form of the invention these homopolymers, copolymers andpolymer blends will have a glass transition temperature of greater than50 degree C., more preferably from about 70 degree C. to about 180degree C., a density greater than 0.910 g/cc and more preferably from0.910 g/cc to about 1.3 g/cc and most preferably from 0.980 g/cc toabout 1.3 g/cc and have from at least about 20 mole % of a cyclicaliphatic or a bridged polycyclic in the backbone of the polymer morepreferably from about 30-65 mole % and most preferably from about 30-60mole %.

In a preferred form of the invention, suitable cyclic olefin monomersare monocyclic compounds having from 5 to about 10 carbons in the ring.The cyclic olefins can selected from the group consisting of substitutedand unsubstituted cyclopentene, cyclopentadiene, cyclohexene,cyclohexadiene, cycloheptene, cycloheptadiene, cyclooctene,cyclooctadiene. Suitable substituents include lower alkyl, acrylatederivatives and the like.

In a preferred form of the invention, suitable bridged polycyclichydrocarbon monomers have two or more rings and more preferably containat least 7 carbons. The rings can be substituted or unsubstituted.Suitable substitutes include lower alkyl, aryl, aralkyl, vinyl,allyloxy, (meth) acryloxy and the like. The bridged polycyclichydrocarbons are selected from the group consisting of those disclosedin the above incorporated patents and patent applications. In apreferred form of the invention the polycyclic hydrocarbon ispolymerized in an addition reaction in preference to a ring openingmetathesis polymerization (ROMP). Suitable bridged polycyclichydrocarbon containing polymers are sold by Ticona under the tradenameTOPAS, by Nippon Zeon under the tradename ZEONEX and ZEONOR, by DalkyoGomu Seiko under the tradename CZ resin, and by Mitsui PetrochemicalCompany under the tradename APEL.

Suitable comonomers include alpha-olefins having from 3 to 10 carbons,aromatic hydrocarbons, other cyclic olefins and bridged polycyclichydrocarbons. It may also be desirable to have pendant groups associatedwith the above-mentioned homopolymers and copolymers. The pendant groupsare for compatibilizing the cyclic olefin containing polymers and thebridged polycyclic hydrocarbon containing polymers with more polarpolymers including amine, amide, imide, ester, carboxylic acid and otherpolar functional groups. Suitable pendant groups include aromatichydrocarbons, carbon dioxide, monoethylenically unsaturatedhydrocarbons, acrylonitriles, vinyl ethers, vinyl esters, vinylamides,vinyl ketones, vinyl halides, epoxides, cyclic esters and cyclic ethers.The monethylencially unsaturated hydrocarbons include alkyl acrylates,and aryl acrylates. The cyclic ester includes maleic anhydride.

It has been found that polymer blends may also be suitable to fabricatethe cassette. Suitable two-component blends of the present inventioninclude as a first component of a COC. The COCs can be present in anamount from about 1 to 99% by weight of the blend, more preferably fromabout 30 to 99%, and most preferably from about 35 to 99 weight percentor any combination or subcombination or ranges therein. In a preferredform of the invention the first components has a glass transitiontemperature of from about 70 degree C. to about 130 degree C. and morepreferably from about 70 to 110 degree C.

The blends further include a second component in an amount by weight ofthe blend of from about 99-1%, more preferably from about 70-1% and mostpreferably from about 65-1%. The second component is selected from thegroup consisting of homopolymers and copolymers of ethylene, propylene,butene, hexene, octene, nonene, decene and styrene. The second componentpreferably has a density of from about 0.870 to 0.960 g/cc and morepreferably from about 0.910 to 0.960 g/cc and more preferably from about0.930 to 0.960 g/cc. In a preferred form of the invention the secondcomponent is and ethylene and alpha-olefin copolymer where thealpha-olefin has from 3 to 10 carbons, more preferably from 4 to 8carbons and most preferably 6 carbons. Most preferably the ethylene andalpha-olefin copolymers are obtained using a metallocene catalyst.

Suitable three-component blends include as a third component a COCselected from those COCs described above and different from the firstcomponent. In a preferred form of the invention the second COC will havea glass transition temperature of higher than about 120 degree C. whenthe first COC has a glass transition temperature lower than about 120degree C. In a preferred form of the invention, the third component ispresent in an amount by weight of from about 10 to 90% by weight of theblend and the first and second components should be present in a ratioof from about 2:1 to about 1:2 respectively of the first component tothe second component.

In a preferred form of the invention, random and block copolymers ofnorbornene and ethylene are selected as the first component of theblend. These norbornene copolymers are described in detail in U.S. Pat.Nos. 5,783,273, 5,744,664, 5,854,349, and 5,863,986. The norborneneethylene copolymer preferably has from at least about 20 mole percentnorbornene monomer and more preferably from about 20 to 75 mole percentand most preferably from about 30 to 60 mole percent norbornene monomeror any combination or subcombination of ranges therein. The norborneneethylene copolymer should have a glass transition temperature of fromabout 70 to 180 degree C., more preferably from 70 to 130 degree C. andeven more preferably from about 70 to 100 degree C.

The second component is preferably an ethylene copolymerized with analpha-olefin having from 4 to 8 carbons. Preferably, the ethylene andalpha-olefin copolymers are obtained using metallocene catalysts.Suitable catalyst systems, among others, are those disclosed in U.S.Pat. Nos. 5,783,638 and 5,272,236. Suitable ethylene and alpha-olefincopolymers include those sold by Dow Chemical Company under the AFFINITYand ENGAGE tradenames, those sold by Exxon under the EXACT tradename andthose sold by Phillips Chemical Company under the tradename MARLEX.

As set forth above, the first component of the norbornene/ethylenecopolymer can be present from about 1 to 99% by weight of the blend,more preferably from about 30 to 99% by weight, and most preferably 35to 99% by weight. In a preferred three-component blend a secondnorbornene and ethylene copolymer is added to the two componentnorbornene-ethylene/ethylene alpha.-olefin blend. The second norborneneethylene copolymer should have a norbornene monomer content of 30 molepercent or greater and more preferably from about 35 to 75 mole percentand a glass transition temperature of higher than 120 degree C. when thefirst component has a glass transition temperature of lower than 120degree C.

The cassette may be fabricated from the COCs and blends set forth above.The cassette may be fabricated from the COCs by injection molding, blowmolding, thermoforming processes or other plastic fabricatingtechniques. In a preferred form of the invention the cassette is formedby injection molding.

The tubing connected to the cassette is compatible with the cassette andis, in a preferred form of the invention, made from a polyolefin andmore preferably from a m-ULDPE and even more preferably from a blend ofm-ULDPE resins in accordance with commonly assigned U.S. Pat. No.6,372,848 which is incorporated in its entirety herein by reference. Thetubing is in fluid communication with the fluid reservoir and can conveyfluid to and from the reservoir.

V. Multiplexing Dialysis Fluid Flow

Referring now to FIGS. 17 to 20, valve and pump arrangement 200illustrates one possible arrangement for the pumps and valves of thepresent invention. FIGS. 18 to 20 set forth a set of values thatillustrate one example of how the valves are sequenced in connectionwith the valve arrangement 200. Other sets of values are thereforepossible.

The cassette-based improvements discussed herein are operable withvarious different types of dialysis therapies, such as hemodialysis andperitoneal dialysis. With peritoneal dialysis, for example, the systemcan be a batch system, a continuous flow system, a tidal flow system andany combination thereof. With batch type systems, dialysis fluid ispumped through the patient and then to drain. Tidal flow systems aremodified batch type systems, wherein instead of pulling all the fluidout of the patient's peritoneal cavity, a portion of the fluid is pulledout more frequently and replaced. Tidal flow systems have propertiessimilar to both batch and continuous therapies.

In continuous flow systems, dialysis fluid is pumped to a patient,through one or more filters and regeneration devices back to thepatient. Continuous flow systems require typically one or moreconcentrates to be added to the fluid before the fluid reaches thepatient. Also, a roughly equal amount of ultrafiltrate produced by thepatient is removed from circulation, so that a total volume of fluidwithin the loop remains relatively constant. The components describedherein can be used likewise in a variable volume CFPD system.

Pump and valve arrangement 200 is operable with each of these types ofsystems. Arrangement 200 is particularly suited for continuous flowtherapies and is described in connection with CFPD accordingly, althoughit is not limited to CFPD. Pump/valve arrangement 200 includes a firstintake valve 202 upstream of a first pump chamber 204 and a firstexhaust valve 206 downstream of pump chamber 204. Pump/valve arrangement200 includes a first intake valve 208 upstream of a second pump chamber210 and a first exhaust valve 212 downstream of second pump chamber 210.

Operating in concert with the first inlet valve 202, a second intakevalve 214 is located upstream of first pump chamber 204. Similarly, asecond exhaust valve 216 is located downstream of first pump chamber204. Operating in concert with first intake valve 208, a second intakevalve 218 is placed upstream of second pump chamber 210. Operating inconcert with first exhaust valve 212, a second exhaust valve 220 islocated downstream of second pump chamber 210.

In a continuous flow system, regenerated dialysis fluid flows from oneor more regeneration device 222, through a first inlet path 226, throughfirst intake valves 202 and 208, to first and second pump chambers 204and 210, respectively. In the continuous flow system, at the same timeor at a slightly different time as discussed in more detail below, oneor more additives or concentrates 228 flows through a second inlet path232, through second intake valves 214 and/or 218, into first and secondpump chambers 204 and/or 210, respectively. Pumps 204 and 210 in anembodiment alternate so that one pump draws in fluid as the second pumppushes fluid to the patient.

In arrangement 200, with respect to continuous flow dialysis, dialysisfluid flows from pumps 204 and 210, through first exhaust valves 206 and212, respectively, through first outlet path 236 to patient 238. Withcontinuous flow, fluid can be discharged alternatively from pumps 204and 210, through second exhaust valves 216 and 220, respectively,through second outlet path 240, to an ultrafiltrate bag 232. In oneembodiment, fluid flows from patient 238, through a regeneration path234, to regeneration device 222.

In automated peritoneal dialysis (“APD”) or in tidal flow, theregeneration device 222 and additives 228 are replaced by one or moresupply bag 224 and 230. Here, pumps 204 and 210 pull fluid alternativelyfrom supply bag 224, through first inlet line 226 and first intakevalves 202 and 208 and/or from supply 230, through second inlet path 232and second intake valves 214 and 218, respectively. In APD or tidalflow, pumps 204 and 210 pump to the patient 238 via first outlet path236, through first exhaust valves 206 and 212. Alternatively, pumps 204and/or 210 can pump via second outlet path 240 through second exhaustvalves 216 and 220, to a sample bag 240 for example.

Thus, with APD or tidal flow, spent fluid is pumped from the patient todrain, so that first outlet path 236 operates as a from patient path andsecond outlet path 240 flows to drain 232. With CFPD, the flow canalternatively be reversed and flow instead from patient 238, throughfirst outlet path 236, to one or both pumps 204 and 210, toultrafiltrate collection 232. Here, first inlet path 226 and firstoutlet path 236 can have multiple lumens to allow flow in bothdirections simultaneously.

For the ease of illustration, the remainder of the present inventionwith respect to Section V is discussed in connection with CFPD. In CFPD,second inlet valves 214 and 218 enable intermittent injection of asecond fluid, e.g., an additive, to the main dialysis fluid flowingcontinuously through first inlet path 226. Second exhaust valves 216 and220 allow for intermittent withdrawal of fluid, e.g., ultrafiltrate,from the main dialysis fluid flowing continuously through first outletpath 236. The second inlet valves 214 and 218 and second outlet valves216 and 220 enable the additional pumping functions to be accomplishedwithout providing additional pumping chambers. Eliminating additionalpumping chambers allows the disposable cassette, and consequently theoverall dialysis machine, to be smaller, lighter and less costly. Theoperation of a machine having a smaller number of pump chambers is alsoless noisy than a machine with a greater number of pump fluid chambers.

FIGS. 18 to 20 illustrate one example of the sequencing of pump 204 and210 and the various valves in connection with arrangement 200 for CFPD.FIG. 18 illustrates the cycling of pumps 204 and 210 with respect to themain flow of dialysis fluid from the regeneration devices 222, throughfirst inlet path 226 and first outlet path 236, to patient 238. In theexample the main dialysate flow through arrangement 200 is set at a rateof 100 ml/minute. In an embodiment, each pump chamber 204 and 210 has atotal volume capability of 10 ml. The pump actuators and pistons 34 areoperated so that one complete pump cycle (both valves performing astroke) occurs every 12 seconds.

FIG. 18 illustrates the volume of fluid being delivered from the pumps204 and 210 to patient 238. During the first six seconds, pump 204 (P1)pumps 10 ml of fluid through valve 206 and first exhaust path 236 topatient 238. First exhaust valve 212 operating with pump 210 is closed.During that same first six seconds, 10 ml of dialysis fluid is pumpedfrom the one or more regeneration devices 222, through first inlet path226, through first intake valve 208, into pump chamber 210. During thissame time, first intake valve 202 is closed.

During the second six seconds or the second half of one complete pumpcycle, pump 210 discharges fluid obtained during the first six secondsto patient 238. Pump 204 pulls fluid from regeneration device 222 inpreparation for pumping to patient 238 in the second pump cycle. Duringthe second six seconds of the first pump cycle, first exhaust valve 212associated with pump 210 is open, while first exhaust valve 206associated with pump 204 is closed. First intake valve 202 associatedwith pump chamber 204 is open, while first intake valve 208 associatedwith pump 210 is closed. Also during the second six seconds of the firstcomplete cycle, pump 210 (P2) delivers 10 ml of fluid to patient 238.The complete cycle is then repeated four more times over a total of oneminute, delivering a total of 100 ml of fluid.

FIGS. 19 and 20 illustrate various possibilities for sequencing thesecond inlet valves 214 and 218 to add one or more additives 228 andsequencing second exhaust valves 216 and 220 to remove ultrafiltrate232, respectively. FIG. 19 illustrates the frequency with which pumps204 and 210 need to pull alternatively from additive 228, through secondinlet path 232, through valves 214 and 218 to achieve a particularflowrate of additive. For example, if it is desired to have an additiveflowrate of one ml/minute, knowing the pump chamber volume to be aconstant 10 ml, a total of one full chamber of dialysate must be pulledthrough pumps 204 and 210 collectively every ten minutes. This meansthat each pump will pump one full chamber of dialysis fluid once everytwenty minutes.

Knowing that there is a total of ten output strokes (both pumps) perminute, each pump 204 and 210 must pump a chamber full of additive 228every one hundred strokes to achieve individually one full chamber onceevery twenty minutes. For a flow of 1 ml of additive per minute when thetotal flow of dialysate to the patient is 100 ml/minute, for pump 204,first intake valve 202 opens ninety-nine consecutive times. Secondintake valve 214 opens on the 100th intake stroke. Likewise, for pump210, first intake valve 208 opens ninety-nine consecutive times. Valve218 opens on the 100th intake stroke.

FIG. 19 illustrates the total chamber volume and stroke sequence foradditive flowrates of 0.2, 0.5, 1.0, 1.5, 2.0 and 3.0 ml/min. It shouldbe appreciated, however, that any desired percentage of additive versusdialysis flow can be achieved via the sequencing of second intake valves214 and 218 with respect to the opening of main inlet valves 202 and208, respectively.

Referring now to FIG. 20, an ultrafiltrate removal table is illustrated.The analysis described above for determining the values in the additivesequencing table FIG. 19 is the same used to determine the values in theultrafiltrate table. Accordingly, to remove one ml per minute of fluidto ultrafiltrate container 232, each of the pumps 204 and 210 pumps onefull chamber volume of 10 ml of fluid once every one hundred strokes toultrafiltrate bag 232 (assuming overall flowrate of dialysis flow is 100ml/minute as shown in FIG. 18). Pumps 204 and 210 pump collectively onechamber volume, e.g., 10 ml of fluid every 10 minutes to achieve anultrafiltrate flowrate of one ml/minute Accordingly, first exhaustvalves 206 and 212 are opened ninety-nine times consecutively.Thereafter, second exhaust valves 216 and 220 are opened upon the 100thstroke.

In both the control of the additive and ultrafiltrate, the opening ofthe second inlet valves 214 and 218 can be spaced apart as desired. Forexample, when the cycle is one every 100 strokes, opening valves 214 and218 can be offset by fifty strokes. In a similar manner, theultrafiltrate can be pulled through second outlet path 240 via valve 216and fifty strokes later through valve 220. It should be appreciated fromFIGS. 19 and 20 that the additive flowrate can be different than theultrafiltrate flowrates. It may be necessary, however, to make up thetotal volume flowing through the loop if the removal rate is larger thanthe additive rate or vice versa. Ultrafiltrate produced by the patientmust also be accounted for, for example, by removing ultrafiltrate at afaster rate than that at which concentrate is added.

In an embodiment, additive 228 and ultrafiltrate 232 are added andremoved, respectively, virtually simultaneously by opening, for example,second inlet valve 214 operating in communication with pump 204 whilesimultaneously opening second exhaust valve 220 operating incommunication with pump 210, when pump 204 is in a pull stroke and pump210 is in a push stroke. This allows additive to be mixed into thesystem simultaneously with ultrafiltrate being pulled from the system ina way such that the additive is not being removed immediately from thepatient loop. It should be appreciated that the pumping order can bereversed so that pump 210 pulls in additive 228, while pump 204discharges ultrafiltrate to container 232.

Partial pump strokes can be used in an embodiment. With a positionablepump actuator, such as the linear or rotational stepper or servo motorin combination with a rotational to linear converter described above inconnection with FIG. 8, it is possible to drive the piston 34 partiallyduring a fill or discharge stroke to pump less than a full pump chambervolume worth of dialysate, additive 228 or ultrafiltrate 232.

The additive flowrate and the ultrafiltrate flowrate can be doubled byopening second intake valves 214 and 218, either simultaneously orduring the same complete pump cycle or opening second exhaust valves 216and 220 simultaneously or within the same overall pump cycle,respectively. The total volume of additive 228 and ultrafiltrate 232 iscalculated knowing the total volume within fluid pumping changes 204 and210, the number of strokes that the second intake and exhaust valves areopened over a given period of time, and the percentage of a strokeemployed (partial stroke or full stroke). As described below inconnection with Section VIII, the volume of fluid pumped canalternatively be measured, for example, using a capacitance fluid volumesensor.

While arrangement 200 has been illustrated with two pumps, it should beappreciated that the multiplexing flow illustrated in connection withFIGS. 17 to 20 is operable with dialysis systems having a single pump orthree or more pumps. Further, while alternating pumps 204 and 210 ispreferred in one embodiment, both pumps can be pulling fluid anddischarging fluid at the same time in an alternative embodiment.Further, where three or more pumps exist, one pump can pull fluid whileone or more pumps pulls fluid, pushes fluid or is idle.

VI. Knowledge-Based Expert Fluid Delivery Systems

Any of the therapies operable with the cassette-based embodiments of thepresent invention (hemodialysis, CFPD, APD and tidal flow peritonealdialysis) may employ multiple pumps, such as two, three, four or evenmore fluid pumps. Also, multiple solutions may be used. Hemodialysispumps blood and dialysate. CFPD uses a number of different solutions,such as the continuously flowing dialysate, a supply of one or moreconcentrated additives, ultrafiltrate produced by the patient, as wellas others. With APD and tidal flow, the systems may employ a pluralityof fluid supply bags operating in parallel.

The various therapies also include a multitude of fluid flowdestinations. Besides the obvious destination of pumping fluid to thepatient, the therapies also pump to an ultrafiltrate container, a drainbag, a sample container, an accumulator or other destination. Thetherapies yield a complex matrix of fluid flow starting points, fluidpumps and fluid flow destinations. Adding to the complexity, automatedsystems allow a multitude of input parameters typically to be varied bythe patient or doctor. The patient or doctor can for example control theoverall therapy time, the fluid flowrate and various dwell periods inconnection with batch systems and a concentration of electrolyte orother additives in a CFPD solution, just to name a few.

It is very difficult if not impossible therefore to predetermine andstore in memory a pumping schedule for each possible combination ofparameters selected by the patient and/or doctor. Accordingly, thepresent invention provides the following expert system and method fordetermining a pumping schedule “on the fly” after the user inputs valuesfor various parameters. The expert system and method for scheduling thepumping of the dialysis therapy is applicable to any combination ofsolutions, pumps, and destinations, such as one or more solutions, oneor more pumps, and one or more destinations. FIG. 21 illustrates onepossibility that includes three solutions, three pumps, and threedestinations.

FIG. 21 illustrates schematically a hardware configuration for: (i)Solution 1 to Solution 3; (ii) pumps P1 to P3; and (iii) Destination 1to Destination 3. To provide a frame of reference, Solution 1 is tabbedas a patient solution, i.e., the solution leaving the patient in CFPD,Solution 2 is an accumulator solution and Solution 3 is a concentratesolution. Destination 1 is tabbed as a filter or cartridge, Destination2 is the accumulator and Destination 3 is an ultrafiltrate container.The CFPD system includes an accumulator in an embodiment thataccumulates a portion of the fluid. The accumulator mixes various fluidsand chemicals and stabilizes those fluids and chemicals. The accumulatorcan also be used to provide a sample of the fluid for analysis. Althougha single chemical concentration additive is illustrated, the dialysissystem, and in particular CFPD, can include many different chemicals andadditives.

As illustrated, the accumulator is both a solution or source and adestination. The designation of a particular entity as a solution ordestination may, in certain instances, be arbitrary, which is allowableas long as the entity is consistently maintained as a solution ordestination. For example, the patient could be either a solution asillustrated, wherein a pump pulls the solution from the patient, or adestination (not illustrated), wherein a pump pushes fluid to thepatient. The patient could further alternatively be a solution and adestination. On the other hand, the concentration solutions cannotalternatively be arbitrarily assigned as a destination. Likewise, theultrafiltrate collection destination cannot otherwise be designated asolution.

FIG. 21 illustrates the various fluid pathways existing for oneembodiment between the solutions, the pumps and the destinations. Asillustrated, Pump 1 can pull from all three solutions but output to onlyDestination 1. This is a physical limitation set by the fluid pathwaysin the disposable cassette and/or by external tubing. Likewise, Pump 2is connected fluidly to be able to pull fluids from any of the threesolutions and to be able to pump to any of the three solutions. Pump 3can only pull fluid from Solution 1 but can pump out to any of the threedestinations. This arrangement is illustrated merely for purposes ofdescribing the expert system of the present invention and can be alteredto achieve any desired configuration.

Referring now to FIG. 22, a state diagram for each of the pumps isillustrated. The state diagram illustrates physical restraints existinginherently in the pumps as well as operational characteristics desiredby the system implementers. For example, the pulling and pushing statesinclude a self-lock that prevents a pump to transition from a pullingstate to another pulling state or from a pushing state to anotherpushing state. This is due to the physical limitations of the pump. Asdescribed above, the pump includes a piston head 36 that pulls apart aflexible membrane from a rigid portion of the disposable cassette topull in fluid and pushes that same membrane towards the rigid portion topush out fluid. Assuming a complete stroke is made (no partial stroke),the pumps are arranged physically so that the next movement afterpulling must be a pushing movement and the next movement after pushingmust be a pulling movement.

Each of the states is allowed to transition, however, to an idlingstate, a characteristic desired by the implementers. When a pump is donepulling, it may do nothing, i.e., idle. When a pump finishes pushing, itmay also do nothing. When a pump is finished idling, it may idle again.A pump may idle for as long as is desired until transitioning to thenext active state based on the previous activity of the state.

FIG. 23 sets forth various rules or restrictions that are placed insoftware to determine, in part, a pumping schedule. The schedule isbased on: (i) the rules of FIG. 23; (ii) various inputs by thedoctor/patient; (iii) a number of calculations based on the inputs; and(iv) a number of constants set for example by the physical limitationsof the system (e.g., pump chamber volume is ten ml). The rules orrestrictions serve to provide a basis upon which a microprocessor of thecontroller of the present invention can make decisions to develop a flowschedule.

Rules 1 to 6 codify the physical flow restraints between the solutions,pumps and destinations illustrated in connection with FIG. 21. FIG. 23does not exhaust all the possible rules that may be derived from thephysical connections between the solutions, pumps and destinations.Rules 1 to 6 set forth merely examples of rules that might beimplemented based on the fluid flow connections.

Rules 7 to 13 set forth certain restrictions that are based on the statediagram of FIG. 22 and other restrictions based on the particulartherapy employed. For example, although the system is connected fluidlyso that Solution 2 can be pumped to Destination 2, Rule 7 in softwareforbids such a flow from taking place. Rules 8 and 9 set forth similarrestrictions.

Rules 12 and 13 designate restrictions that simplify the calculationsmade to generate the flow schedule. Rule 12 specifies that a pump pumpsonly from one source during any giving pulling stroke. Rule 13designates that a pump delivers fluid to only a single destinationduring a pump discharge stroke. These rules do not conflict with themultiplexing flow of Section V, wherein the pumps pump dialysate for anumber of complete strokes and then pump an additive or ultrafiltratefor one or more complete strokes. One alternative embodiment in SectionV does, however, include partial strokes which may or may not involvepumping fluid from more than one source or pumping fluid to more thanone destination during a given stroke. The expert system can be modifiedto include such partial strokes; however, certain of the algorithmsdiscussed below would be more complicated.

FIG. 24 sets forth one outcome from the diagrams and rules of FIGS. 21to 23. FIG. 24 illustrates three function modules 244, 246 and 248 thatprovide the controller with three options based on Rule 1 illustratedabove in FIG. 23. That is, Rule 1 allows pumping to occur from Solution1, through Pump 1 to Destination 1, as indicated by function module 244;pumping to occur from Solution 1, through Pump 2 to Destination 1,according to function module 246; and pumping to occur from Solution 1,through Pump 3 to Destination 1, as indicated by function module 248.Each of the function modules 244, 246 and 248 also requires that thepumping be maintained within specified pressure limits. The pumping iscontrolled to occur over a designated period of time, moving theflexible membrane of the cassette at a particular velocity and movingthe third under a specified pressure limit.

FIG. 24 illustrates three possible ways to accomplish moving fluid fromSolution 1 to Destination 1, e.g., from the patient to the filter.Depending on other fluid pumping actions taking place simultaneously,one or more of the function modules 244, 246 and 248 may be eliminateddue to other rules, such as rules restricting: (i) pumping from the samesolution to two pumps at the same time; (ii) pumping two differentsolutions using the same pump at the same time; (iii) pumping to twodifferent destinations using the same pump at the same time; or (iv)pumping from two pumps to the same destination at the same time. Thus,the schedule at a particular point in time may have to choose one of thethree function modules 244, 246 and 248.

Alternatively, the controller can choose to pump from Solution 1 toDestination 1 at a different point in time, for example, if all threepumps are already assigned to another pumping assignment. Thecontroller, however, is also bound by the therapy parameters thatrequire a certain amount of fluid to be pumped from the patient to thefilter over a certain amount of time. The controller cannot thereforedelay the pumping from Solution 1 to Destination 1 for too long aperiod. It should be appreciated from this illustration that the rulesand inputted parameters cooperatively provide the controller with aframework upon which to generate a pumping flow schedule.

FIGS. 25 and 26 illustrate high level process flow diagrams 250 and 260that show the control of the various pumps prior to and after developingthe flow schedule, respectively. Process flow diagram 250 illustratesthe generation of the pumping schedule. Process flow diagram 260illustrates the actuation of the pumping schedule.

Upon starting therapy as indicated by oval 252, the patient or doctorsupplies values for various input parameters, as indicated by block 254.Input devices, such as devices 184 shown in FIG. 12, can be used forexample to select a value for a parameter from a range of possiblevalues. Otherwise, the patient or doctor can type or key a value using atouch screen or hand key pad.

FIG. 27 illustrates various input parameters 272, such as the strokevolume (this can alternatively be a constant, e.g., 10 ml, as describedabove in connection with the multiplexing Section VI). The patient ordoctor enters the total therapy time, which as illustrated in FIG. 27is, for example, 480 minutes. The dialysis fluid flowrate is inputted tobe 250 ml/minute in the example of FIG. 27. Concentrate is added at aflowrate of 5 ml/minute and ultrafiltrate is removed at a flowrate of 2ml/minute. The patient or doctor enters the amount of ultrafiltrate thatis expected to be generated by the patient, which is 2 ml/minute forexample. The patient or doctor also enters a ratio (R) between thedialysate flowing through the main regeneration loop and flowing throughan accumulator loop. FIG. 27 merely sets forth examples of inputs. Thedoctor or patient can make other types of inputs alternatively oradditionally.

After providing the necessary inputs as indicated by block 254, thesystem and method performs a number of calculations based on theinputted information, as indicated by block 256. The calculations alsouse a number of constants and/or other variables. FIG. 28 illustratesvarious algorithms or formulas used by the expert system of the presentinvention to generate the outcomes needed, as indicated by block 256, todevelop a knowledge-based schedule for pumping.

The equations 274 include calculating a cycle time, which is equal tothe total therapy time divided by a number of cycles. In an embodiment,the schedule outputted is a portion of the total pumping schedule. Theschedule is therefore repeated or cycled a number of times to achievethe overall goals of the therapy. Equations 274 also include a stroketime that is a function of the stroke volume and the dialysate flowrate.The system calculates a number of patient pump strokes, which is afunction of the cycle time and the stroke time. An accumulator flowrateis calculated knowing the dialysate flowrate and the ratio R describedabove in connection with the inputs 272 of FIG. 27.

The number of accumulator strokes (number indicates to or from, notboth) is equal to the cycle time multiplied by the accumulator flowrate,which is divided by the stroke volume. A number of strokes cyclespulling from the concentration source is calculated via the cycle timemultiplied by the inputted concentration flowrate, which is divided bythe constant stroke volume. The number of ultrafiltrate strokes is afunction of the cycle time, the inputted ultrafiltrate removal rate, theinputted concentrate addition flowrate and the stroke volume. It shouldbe appreciated that additional or alternative equations may be used.Equations 274 of FIG. 28 are illustrated merely to describe the expertsystem and method of the present invention.

FIG. 29 illustrates the outputs needed to generate the pumping schedule,as indicated by block 256 in FIG. 25. Outputs 276 are based on or areapplied to the entire therapy or are otherwise constant throughout theentire therapy. Outputs 278 are based on or applicable to a singlecycle. For example, assuming the desired number of cycles is 48(schedule repeated 48 times) and the total therapy time is 480 minutes,the time for each cycle is ten minutes. The outputs 276 are based on thetotal therapy time of 480 minutes in the illustrated embodiment, whileoutputs 278 are based on a cycle time of 10 minutes.

Regarding outputs 276, the recirculation stroke number of 12,000 is thetotal number of times any of the three pumps (three pumps collectively)pump from the patient. In a similar manner, the number 4,000 representsthe number of strokes that the three pumps make collectively to theaccumulator. The pumps pump collectively another 4,000 strokes from theaccumulator. The pumps in combination pump from the one or moreconcentration sources a total of 240 times over the therapy. The pumpsin combination pump to the ultrafiltrate container a total of 336 timesduring the therapy. The difference in volume produced by the fromconcentrate and to ultrafiltrate strokes is due, at least in part, to avolume of ultrafiltrate produced by the patient.

The outputs 278 are based on the ten minute cycle and coverapproximately 1/48th of the time of the outputs 276, which cover theentire 480 minute therapy time. The final two outputs 278 set forth thenumber of strokes (248) to Destination 1, i.e., to the cartridge orfilter. The last illustrated number (338) is the total number of fillstrokes over the 10 minutes, which is a combination of the 250 patientstrokes, the 83 from accumulator strokes and the five strokes fromconcentrate.

After performing the calculations and achieving the needed outputs asindicated by block 256, the expert system uses the calculated outcomes,the rules, the state diagram and the function modules set forth above toproduce a pumping schedule, as indicated by block 258. The controlleruses the schedule to control X number of pumps, for Y number ofsolutions and Z number of destinations, wherein X, Y and Z can each beone or greater. A portion of a sample schedule is illustrated in FIG.30. Based on the information provided above, knowing that a stroke timeis 2.4 seconds and each cycle lasts 10 minutes, the schedule 280 has twohundred fifty entries 282. For ease of illustration, twenty-five entriesor one minute's worth of pumping is illustrated. In actuality, theschedule includes two hundred twenty-five additional entries 282 (asindicated by dots), i.e., nine additional minutes worth of pumping.

Schedule 280 includes a column for each of the solutions discussed abovein connection with FIG. 21, namely, the patient solution, theaccumulator solution, and the concentrate solution. Schedule 280includes a column for each of the destinations discussed above inconnection with FIG. 21, namely, the cartridge or filter, theaccumulator and the ultrafiltrate container. Using the rules, desiredoutputs and ensuring that no pressure limit is exceeded, the controllergenerates the schedule of entries 282 as illustrated in FIG. 30.According to the first entry 282, during the first 2.4 seconds, Pump 2makes one complete stroke pulling fluid from the patient, Pump 1 makesone complete stroke pulling fluid from the concentration, and Pump 3makes one complete stroke pushing fluid to the ultrafiltrate container.In the next 2.4 seconds, the pumps maintain a different profile. As isseen readily, in various entries 282 less than all three of the pumpsare activated. Any percentage of the pumps can be activated in any ofthe entries 282.

Schedule 280 allows other rules to be implemented. For example, theschedule can apportion equal pumping strokes for each pump over thetotal therapy or over a cycle, so that the pumps wear approximatelyevenly. Other rules may be implemented to rest a pump after a particularnumber of strokes, so that the pump can, for example, purge air orperform any necessary resetting function.

After generating the pumping schedule as indicated by block 258, thecontroller implements the pump schedule to achieve the desired flowratesand the desired overall fluid pumping volumes as indicated by processflow diagram 260 of FIG. 26. The system finds the next entry 282 of thepumping schedule as indicated by blocks 262. At the start of therapy orthe start of a cycle within the therapy, the next entry is the firstentry 282. Also, as determined in connection with diamond 264, theprevious entry may have been the last entry. Otherwise, if the previousentry is not the last entry of the particular cycle table, the systemperforms the pumping state, e.g., pulling, idling, or pushing, for eachof the three pumps, as indicated by block 266. Afterward, the systemreturns to block 262 and the current cycle is carried out until theschedule reaches the end, as indicated by diamond 268. When the cyclereaches its end, the system determines whether the schedule is repeatedor not. As discussed above, the schedule represents one cycle of aplurality of cycles, e.g., ten cycles. If another cycle is required tocomplete the therapy as determined in connection with diamond 268, theentire sequence of process flow diagram 260 is repeated. If the totalnumber of cycles has been completed as determined in connection withdiamond 268, the therapy is ended, as indicated by oval 270.

VII. Integral Port Vent

Referring now to FIG. 31, various embodiments for cassette-based portvents of the present invention are illustrated. The disposable cassettesdescribed herein include a vent port having a venting membrane. Themembranes vent the priming volume (air existing in tubes before thestart of therapy) and gasses generated during therapy. The cassette isprovided with an air sensor, for example, a capacitance fluid sensordescribed below, which detects when air or other gases enter the system.When air or other gases, or a particular level thereof, enters thesystem, the controller of the system (not illustrated) vents the air orgases through a vent, such as vent 285 or 295.

The cassette has a portion shown above as reference numbers 92, 162 and192, which are made of a rigid or semi-rigid plastic material asdescribed above (referred collectively as rigid portion). Rigid portions92, 162 and 192 define a plurality of holes or apertures 284 and slots286. Apertures 284 operate, via one of the flexible membranes, withvalve plungers 42 in an embodiment. Slots 286 form fluid or gas pathwayswhen enclosed by the membranes 94 and 96. Certain slots lead to aventing port, such as port vents 285, 295, 297 and 299. The slots 286communicate fluidly in an embodiment with a patient fluid line, aregeneration device for CFPD, a fluid supply for APD or other therapycomponent. Port vents 285, 295, 297 and 299 are operable with each ofthe therapies described herein.

Port vents 285, 295, 297 and 299 are alternative embodiments. Vents 285and 295 include an extension that is formed integrally with the rigidportion 92, 162 or 192 of the associated disposable cassette. Vents 285and 295 extend from sidewall 288. Vents 297 and 299 include aperturesthat are formed integrally with the rigid portion of the cassette. Portvent 297 for example is formed in sidewall 288 of the rigid portion. Forconvenience, the upper flexible membrane has been removed from the rigidportion to illustrate the holes 284, slots 286 and to better see Vent299. Lower flexible membrane 96 is illustrated, adhered or sealed to therigid portion.

Port vent 285 includes a flared port 292 that extends integrally fromsidewall 288. Thus when rigid portion 92, 162 or 192 is formed, e.g.,molded or extruded, to have the apertures 284 and slots 286, the flaredport 292 is also formed. Port 292 defines a hole that communicatesfluidly with a hole defined by sidewall 288, the port hole and sidewallhole in turn communicating fluidly with one of the slots or fluidpathways 286. Although port 292 is shown having a conical or flaredshape, it should be appreciated that port 292 includes any suitableshape, such as a straight cylindrical shape, hose barbed shape or othershape that lends itself to being coupled to the filter 290.

Filter 290 is disposed on and supported by integral port 292 via anysuitable method, such as adhering, heat sealing, mechanically attachingand any combination thereof, for coupling filter 290 to port 292. Forany of the vent embodiments described herein, filter 290 is or includesa hydrophobic membrane. One suitable hydrophobic membrane is made byMillipore, 80 Ashby Road, Bedford, Mass. 01730. Alternatively, thefilter is made from a material such as polytetrafluorethylene (“PTFE”),Teflon, nylon, polyethylene, polypropylene, polystyrene,polyvinylchloride (“PVC”), polyvinylidene, a polyamide, Gortex and anycombination of these. In an embodiment, the filter has a pore size ofbetween zero and one micron, and in one preferred embodiment about 0.2micron. A pore size of 0.2 micron is suitable to vent the priming volumeand exhaust gases generated during therapy.

Alternative port vent 295 also includes an integrally formed flared port296 that can alternatively be any of the shapes described above for port292. Any of the embodiments for the filter 290 can also be used withport vent 295. The filter 290 is bonded, sealed or mechanicallyconnected to a bushing 294. The bushing 294 can be a section of tubingor pipe of the same or different material as rigid portion 92, 162 and192 and consequently of the same or different material as port 296.Bushing 294 is adhered, sealed or mechanically attached to integral port296. In an embodiment, bushing 294 is removably attached to port 296,e.g., via mating threads.

Alternative vents 297 and 299 do not include an integrally formed port,such as ports 292 and 296. Instead, a feature of rigid portion 92, 162,192 defines an opening sized to house a filter 290. For vent 297,sidewall 288 defines an aperture into or onto which filter 290 isfilled. Filter 290 can be attached to sidewall 288 via any of themethods discussed above. A separate collar or cover (not illustrated)can be provided for additional support.

Vent 297 is disposed vertically. Vent 299 is disposed horizontally on orwithin a shape or feature defined by the rigid portion. The shape orfeature is formed integrally as a hole 284 or slot 286. The hole or slothouses or supports filter 290 of vent 299 via any of the methods ofattachment described above. Further, upper flexible membrane 94 can sealaround or to an outer portion of filter 290 to provide additionalmounting support for vent 299.

As described above, one or more pumps is connected fluidly to one ormore solution supplies and one or more solution destinations. Thepumping of the fluid may inadvertently entrain air within the fluid.Also ultrafiltrate produced by the patient may contain various off-gasesfrom the peritoneal cavity. When the filter 290 is made of a hydrophobicmaterial, i.e., one that allows air but not fluid escape therefrom, theport vents 285 and 295 can communicate directly with a fluid pathway,such as via one of the slots 286. Here, the filter 290 holds thepressure of the fluid pump. If the filter is not capable of separatingair from fluid, the port vents 285 and 295 are alternatively connectedto air flow lines that contain vent gases but not fluid. Such air flowlines can be achieved for example via fluid sumps and chambers thatcollect fluid at the bottom and collect air or other gases at the top.One such chamber is shown below in connection with FIG. 32. In FIG. 31,slots 286 that communicate with ports 292 and 296 of vents 285 and 295,respectively, and directly with vents 297 and 299 are alternatively airvent slots 286 rather than fluid pathways.

VIII. Air Separation Chamber

Referring now to FIG. 32, one embodiment of an air separation chamber300 having a capacitance fluid volume sensor is illustrated. Thecapacitance sensor is also discussed in connection with a fluid pump inpatent application entitled, “Capacitance Fluid Volume Measurement,”Ser. No. 10/054,487, filed on Jan. 22, 2002, incorporated herein byreference. The capacitance sensor in operation with the fluid pumpenables air entrained in the medial fluid to be sensed and expelled atthe time of pumping. The pumping cassette-based air separation chamberoperates with the cassette-based port vents 285, 295, 297 or 299described in Section VII.

The pumping cassette-based air separation chamber fluid is placedtypically upstream of a fluid heater. In an embodiment, the cassettealso defines a fluid heating path that receives fluid from one or moreof the pumps. The pump or cassette-based air separation chamber is notable to remove air introduced into the fluid due to heating because thechamber operates upstream of the heater. Air separation chamber 300 istherefore placed downstream of the heater, e.g., downstream of thecassette, in one embodiment and removes air entrained in the medialfluid due to heating. The fluid leaving chamber 300 is pumped via apatient line to the patient. Both the pump-based separation chamber andthe chamber 300 of FIG. 32 are operable while the system pumps fluid anddo not require the system to stop to purge gas. It should beappreciated, however, that air separation chamber 300 is operable withmedial fluid systems, such as dialysis systems, either upstream,downstream or upstream and downstream from the fluid heater.

The capacitance sensor uses capacitance measurement techniques todetermine the volume of a fluid, including air, inside of a chamber. Asthe volume of the fluid changes, a sensed voltage that is proportionalto the change in capacitance changes. Therefore, the sensor candetermine whether the chamber is, for example, empty, an eighth full,quarter full, half full, full, or any other percent full of fluid orair. Each of these measurements can be made accurately, for example, atleast on the order of the accuracy achieved by known gravimetric scalesor pressure/volume measurements. The capacitance sensor, is simple,non-invasive, inexpensive and accurate.

Generally, the capacitance C between two capacitor plates changesaccording to the function C=k*(S/d), wherein k is the dielectricconstant, S is the surface area of the individual plates, and d is thedistance between the plates. The capacitance between the plates changesproportionally according to the function 1/(R×V), wherein R is a knownresistance and V is the voltage measured across the capacitor plates.

The dielectric constant k of medical fluid or dialysate 302 is muchhigher than that of air or gas 304. As more air becomes trapped insidechamber 300, the overall dielectric changes from a higher dielectricdialysate to a lower dielectric air due to the increasing amount of airbetween conductive plates 306 and 308. Capacitance plates 306 and 308are disposed inside an insulative or dielectric housing 310 in anembodiment. The conductive plates 306 and 308 are located closer to aninner surface of housing 310 than an outer surface of the housing.

As housing 310 of chamber 300 fills with medical fluid or air, theoverall capacitance changes, i.e., increases or decreases, respectively.The sensor generates a high impedance potential across the active andgrounded capacitor plates 306 and 308, respectively. The high impedancepotential is indicative of an amount of fluid, such as dialysate or air,in housing 310. Housing 310 is made from an inert, medically safeelectrically insulative material, such as polytetrafluorathelene(“PTFE”), Teflon, nylon, polyethylene, polypropylene, polystyrene,polyvihydrochloride (“PVC”), polyvinylidene, a polyimide and anycombination of these.

A capacitance sensing circuit (not illustrated) amplifies the highimpedance signal to produce a low impedance potential. The low impedancepotential is also fed back to a guard plate 312, which protects thesensitive signal from being effected by outside electrical influences.The amplified potential is converted to a digital signal and fed to asystem processor (not illustrated), where it is filtered, convertedand/or summed A video monitor 176 (FIG. 12) provides visually a volumeand/or a flowrate indication to a patient or operator in an embodiment.Additionally, the processor controls one or more pumps and/or valves ofthe system, for example, to terminate dialysate flow upon reaching apredetermined overall volume or to shut off flow if a particular amountof air is sensed.

In the illustrated embodiment, the housing 310 of chamber 300 forms aclamshell with first and second portions corresponding to conductiveplates 306 and 308. Spherical, cubical, rectangular or other shapes arepossible for housing 310. The portions of housing 310 form a rigid,fixed volume, clamshell shape. The portions can be formed integrallytogether or fixedly or removably sealed together.

Housing 310 defines inlet and outlet ports 314 and 316, respectively.Inlet port 314 enables medical fluid 302, for example, dialysate, toenter the chamber 300, while outlet port 316 enables medical fluid 302to exit chamber 300. In the embodiment illustrated, outlet port 316resides at the bottom of housing 310 of chamber 300 to allow the heaviermedical fluid 302 to separate from any air 304 entrained therein. Theair 304 as illustrated tends to collect towards the top of housing 310.In alternative embodiments, inlet port 314 and outlet port 316 can belocated at different areas of housing 310 and have various orientationswith respect to one another.

Inlet ports 314 and 316 can have any configuration known to those ofskill in the art for connecting sealingly to inlet tube 318 and outlettube 320, respectively. Ports 314 and 316 can be a straight tube (asillustrated), angular tube, hose barb, compression fitting, threaded orother configuration. Inlet and outlet ports can be of the same size orsized differently and be sized for a standard size inner tube diameterof tubes 318 and 320. Tubes 318 and 320 run to various places inaccordance with the particular therapy.

A baffle 322 is provided inside housing 310 and near inlet 314 todeflect incoming fluid 302 upward or away from outlet port 316. Baffle322 facilitates and enhances the separation of air 304 from fluid 302.Baffle 322 reduces the likelihood that air will exit through outlet port316. Baffle 322 tends to direct air or gas bubbles upward so that thebubbles have to change direction to exit outlet port 316. Baffle 322 canbe formed integrally with housing 310 or be attached via a medicallysafe adhesive, via an attachment mechanism, heat sealed, sonicallysealed or attached via methods otherwise known to those in the art.Baffle 322 can have any desired shape and be configured to fit the shapeof housing 310. In an alternative embodiment, multiple baffles 322 areprovided. A second one or more baffle 334 can be suitable placed nearvent port 324 to help stop fluid from exiting housing 310.

Housing 310 defines air venting port 324 in an embodiment.Alternatively, any of the ports 314, 316 and 324 are separate piecesthat attach in a suitable manner to housing 310. Air vent port 324 canbe of a same or different size as inlet and outlet ports 314 and 316 andcan have any of the configurations described above in connection withports 314 and 316 for sealing to air vent tube 326. Air 304 or othergases, such as gases formed within the peritoneal cavity or gases usedto pressurize the system, escape housing 310 and chamber 300 via ventingport 324.

Vent tube 326 connects in an embodiment to various flow control andfluid control devices. One or more valves 328 are connected fluidly withvent tube 326. In an embodiment, one or more of the valves 328 aresolenoid or electrically operated valves, which are opened or closed bythe system processor based on a signal produced via capacitance plates306 and 308. One or more of valves 328 can alternatively be operatedmanually. A sump or fluid trap 330 is provided additionally in anembodiment upstream, between or downstream of valves 328 to collect anyfluid that escapes through vent port 324. An additional solenoid ormanual valve 328 is provided downstream of sump 330 in an embodiment toallow the sump or fluid trap to drain.

A venting membrane 332 is placed at the end of vent tube 326. Ventingmembrane 332 can be of any type known to those of skill in the art. Inan embodiment, venting membrane 332 is a hydrophobic membrane thatenables air 304 but not fluid 302 to escape from venting tube 326.Alternatively, valves 328 and sump 330 may keep moisture from contactingmembrane 332 sufficiently that membrane 332 is designed for contact withgas only. In one embodiment, air or gas 304 can escape from chamber 300through membrane 332 but cannot enter chamber 300 through membrane 332.Membrane 332 can be made of any of the materials described above for thefilter 290 of FIG. 31.

In operation, the capacitance sensor generates a signal or voltageproportional to or indicative of the amount of fluid 302 or air 304within the housing 310 of chamber 300. When a predetermined amount ofair or gas 304 is detected, the processor opens one or more valves 328to allow the gas or air 304 to discharge or be purged from the housing310 of chamber 300. After a certain amount of time or after a particulardielectric or voltage is sensed, the processor closes the one or morevalves 328. This cycle is repeated throughout the medical delivery,e.g., dialysis therapy. In an embodiment, if a particular amount of gasis sensed, the system enters an alarm condition, wherein fluid pumpingstops until a safe fluid level is reached.

In an alternative embodiment, multiple capacitance sensors, i.e.,multiple sets of plates 306, 308 and 312 are used. The sensors producecollectively an output indicative of an amount of fluid 302 or air 304,which is used to open or close valves 328. The valves 328 are controlledvia the collective signal as described above.

In a further alternative embodiment, an air separation device 400 isprovided. Device 400 includes two valves 328 operating in series with afluid trap 330 placed between valves 328. Device 400 does not requirethe remainder of chamber 300. The controller (not illustrated) commandsvalves 328 at certain points in time to open sequentially, out of phase,so that any fluid that escapes with the volume of gas flowing betweenthe valves can flow to trap 330. The pressure of fluid 302 pressurizesair or gas 304 trapped between valves 328. Outer valve 328, adjacent tomembrane 332, is opened to relieve pressure between the valves 328 andallow the excess gas to escape. Membrane 332 is optional. Valve 328downstream of fluid trap 330 is provided to allow fluid to drainautomatically. Device 400, like chamber 300, can operate while the fluidpumps are in operation and does not require the pumps to be shut downintermittently. Device 400 can be cassette-based in an embodiment andplaced upstream and/or downstream of the fluid heater.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present invention andwithout diminishing its intended advantages. It is therefore intendedthat such changes and modifications be covered by the appended claims.

The invention is claimed as follows:
 1. A peritoneal dialysis method comprising: enabling a disposable pumping cassette to be aligned so that (i) a soft side of the disposable pumping cassette faces towards a vacuum chamber and a rigid piston head of a peritoneal dialysis machine, the rigid piston head attached to a rigid piston shaft that is connected mechanically to a stepper motor via a coupler, and (ii) a dialysis fluid supply line, a patient line and a drain line extend from a hard part of the disposable cassette to the outside of the peritoneal dialysis machine and communicate with a respective dialysis fluid supply container, a patient and a drain; positioning the rigid piston head relative to the vacuum chamber such that the rigid piston shaft translates back and forth within the vacuum chamber; applying a vacuum from a negative pressure source communicating pneumatically through the vacuum chamber such that the soft side of the disposable pumping cassette is pulled into contact with a surface of the rigid piston head to at least partially mate the soft side of the disposable pumping cassette with the rigid piston head; operating a stepper motor such that the rigid piston head and the soft side of the disposable pumping cassette extend at least partially into the hard part of the disposable pumping cassette so as to push (i) fresh dialysis fluid from the disposable pumping cassette, through the patient line or (ii) used dialysis fluid from the disposable cassette, through the drain line and to the drain; and operating the stepper motor such that the rigid piston head retracts from the hard part of the disposable pumping cassette while the negative pressure source applies a vacuum through the vacuum chamber to the soft side of the disposable pumping cassette to hold the soft side in at least partial contact with the surface of the rigid piston head so as to draw (i) fresh dialysis fluid from the dialysis fluid supply container through the supply line and into the disposable pumping cassette through the supply line or (ii) used dialysis fluid from the patient through the patient line and into the disposable pumping cassette.
 2. The peritoneal dialysis method of claim 1, which includes retracting the rigid piston head completely out of the hard part of the disposable pumping cassette and alternating the soft side of the disposable pumping cassette to move away from the hard side of the disposable pumping cassette.
 3. The peritoneal dialysis method of claim 1, which includes extending the rigid piston head at least partially into the hard part of the disposable pumping cassette by a preset distance using the stepper motor.
 4. The peritoneal dialysis method of claim 1, which includes enabling the disposable pumping cassette to be aligned with the peritoneal dialysis machine at a non-vertical angle.
 5. The peritoneal dialysis method of claim 1, which includes conforming the shape and size of the rigid piston head to a shape and size of a pump chamber portion of the hard part of the disposable cassette.
 6. The peritoneal dialysis method of claim 1, which includes positioning the rigid piston head relative to the vacuum chamber such that the rigid piston shaft moves back and forth sealingly within the vacuum chamber.
 7. The peritoneal dialysis method of claim 1, which includes configuring the disposable cassette so that when accepted by the peritoneal dialysis machine multiple dialysis fluid supply lines extend from a same surface of the peritoneal dialysis machine.
 8. A peritoneal dialysis method comprising: enabling the mating of a disposable pumping cassette with a peritoneal dialysis machine having first and second rigid piston heads attached to first and second respective rigid piston shafts; operating a stepper motor such that the first and second rigid piston shafts are moved within a vacuum chamber towards the disposable pumping cassette and the first and second respective rigid piston heads contact and move first and second respective portions of a flexible membrane of the disposable pumping cassette into a rigid portion of the disposable pumping cassette to push (i) fresh dialysate out of the disposable pumping cassette, through a patient line towards a patient or (ii) used dialysate out of the disposable pumping cassette, through a drain line towards a drain; and using a negative pressure source communicating pneumatically through the vacuum chamber to apply (a) a first vacuum mating the first portion of the flexible membrane to a surface of the first rigid piston head and (b) a second vacuum mating the second portion of the flexible membrane to a surface of the second rigid piston head, causing the first and second portions of the flexible membrane to respectively follow the first and second rigid piston heads as either rigid piston head is moved away from the disposable pumping cassette to pull (i) fresh dialysate from a fresh dialysate supply line into the disposable pumping cassette or (ii) used dialysate from the patient line to fill a respective first or second pump chamber of the disposable pumping cassette.
 9. The peritoneal dialysis method of claim 8, which in a first stroke includes moving the first rigid piston head towards the disposable pumping cassette to push fresh dialysate through the patient line or used dialysate through the drain line while moving the second rigid piston head away from the disposable pumping cassette to pull fresh dialysate from the dialysate supply line or used dialysate from the patient line, respectively.
 10. The peritoneal dialysis method of claim 9, which in a second stroke includes moving the first rigid piston head away from the disposable pumping cassette to pull fresh dialysate from the dialysate supply line or used dialysate from the patient line, while moving the second rigid piston head towards the disposable pumping cassette to push fresh dialysate through the patient line or used dialysate through the drain line, respectively.
 11. The peritoneal dialysis method of claim 8, which includes prompting a fluid connection of the patient line to an indwelling patient catheter after mating the disposable pumping cassette to the peritoneal dialysis machine.
 12. The peritoneal dialysis method of claim 11, which includes moving the first and second rigid piston heads and applying the first and second vacuums to prime the disposable pumping cassette with fresh dialysate prior to prompting the fluid connection.
 13. A peritoneal dialysis method comprising: applying a vacuum to a pumping portion of a flexible membrane of a dialysis fluid carrying pumping cassette aligned with a vacuum chamber, the vacuum generated from a negative pressure source communicating pneumatically with the vacuum chamber; turning a stepper motor shaft a controlled amount to move a rigid piston shaft and a rigid piston head attached to the rigid piston shaft such that the rigid piston head contacts and moves the pumping portion of the flexible membrane into the dialysis fluid carrying pumping cassette, thereby causing (i) fresh dialysis fluid to be pushed out of the dialysis fluid carrying pumping cassette, through a patient line connected to a patient connector or (ii) used dialysis fluid to be pumped out of the dialysis fluid carrying pumping cassette, through a drain line connected to a drain; and turning the stepper motor shaft in an opposite direction a controlled amount to move the rigid piston shaft and the rigid piston head such that the rigid piston head retracts within the pumping portion of the flexible membrane of the dialysis fluid carrying pumping cassette, the vacuum generated from the negative pressure source causing the flexible membrane to follow a surface of the rigid piston head as the rigid piston head is retracted, so as to draw fresh dialysis fluid into the dialysis fluid carrying pumping cassette from a fill line connected to a dialysis fluid source or used dialysis fluid into the dialysis fluid carrying pumping cassette from the patient line.
 14. The peritoneal dialysis method of claim 13, which includes directly contacting the pumping portion of the flexible membrane with the piston head when moving the piston head into the pumping cassette.
 15. The peritoneal dialysis method of claim 13, which includes retracting the rigid piston head completely away from a rigid portion of the dialysis fluid carrying pumping cassette.
 16. The peritoneal dialysis method of claim 13, which includes connecting the drain line to a drain before moving the rigid piston head towards the dialysis fluid carrying pumping cassette.
 17. The peritoneal dialysis method of claim 13, which includes communicating the negative pressure source with the vacuum chamber via a channel defined in at least one of the rigid piston shaft and the rigid piston head.
 18. The peritoneal dialysis method of claim 17, which includes rotatably sealing the rigid piston shaft to an opening in the vacuum chamber.
 19. The peritoneal dialysis method of claim 13, which includes connecting the patient line to a patient transfer set before moving the rigid piston head into the dialysis fluid carrying pumping cassette.
 20. The peritoneal dialysis method of claim 13, which includes coupling the dialysis fluid carrying pumping cassette to the peritoneal dialysis machine at a non-vertical angle. 